CN105797139A - Application of PTH combining SDF-1 in preparing medicine for improving periodontal tissue regeneration - Google Patents
Application of PTH combining SDF-1 in preparing medicine for improving periodontal tissue regeneration Download PDFInfo
- Publication number
- CN105797139A CN105797139A CN201610252121.4A CN201610252121A CN105797139A CN 105797139 A CN105797139 A CN 105797139A CN 201610252121 A CN201610252121 A CN 201610252121A CN 105797139 A CN105797139 A CN 105797139A
- Authority
- CN
- China
- Prior art keywords
- sdf
- pth
- periodontal
- application
- cell
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 title claims abstract description 86
- 101710088580 Stromal cell-derived factor 1 Proteins 0.000 title claims abstract description 85
- 239000003814 drug Substances 0.000 title claims abstract description 16
- 230000017423 tissue regeneration Effects 0.000 title claims abstract description 12
- 230000003239 periodontal effect Effects 0.000 title abstract description 21
- 102000008186 Collagen Human genes 0.000 claims abstract description 16
- 108010035532 Collagen Proteins 0.000 claims abstract description 16
- 229920001436 collagen Polymers 0.000 claims abstract description 16
- 108090000445 Parathyroid hormone Proteins 0.000 claims description 59
- 239000012528 membrane Substances 0.000 claims description 22
- 230000008439 repair process Effects 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 8
- 208000028169 periodontal disease Diseases 0.000 claims description 5
- 102100036829 Probable peptidyl-tRNA hydrolase Human genes 0.000 claims 3
- 210000000130 stem cell Anatomy 0.000 abstract description 21
- 230000000694 effects Effects 0.000 abstract description 18
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- 230000004069 differentiation Effects 0.000 abstract description 5
- 230000004888 barrier function Effects 0.000 abstract description 2
- 230000000704 physical effect Effects 0.000 abstract description 2
- 230000035755 proliferation Effects 0.000 abstract description 2
- 230000011164 ossification Effects 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 102100036893 Parathyroid hormone Human genes 0.000 description 54
- 210000004027 cell Anatomy 0.000 description 19
- 210000000988 bone and bone Anatomy 0.000 description 14
- 230000007547 defect Effects 0.000 description 12
- 230000006378 damage Effects 0.000 description 11
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 10
- 101710082513 C-X-C chemokine receptor type 4 Proteins 0.000 description 10
- 210000002379 periodontal ligament Anatomy 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 9
- 101710189683 Alkaline protease 1 Proteins 0.000 description 7
- 101710154562 Alkaline proteinase Proteins 0.000 description 7
- 101710170876 Antileukoproteinase Proteins 0.000 description 7
- 101710112538 C-C motif chemokine 27 Proteins 0.000 description 7
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 7
- 102100037011 RNA cytidine acetyltransferase Human genes 0.000 description 7
- 238000004043 dyeing Methods 0.000 description 7
- 238000011160 research Methods 0.000 description 7
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 210000002216 heart Anatomy 0.000 description 5
- 230000008929 regeneration Effects 0.000 description 5
- 238000011069 regeneration method Methods 0.000 description 5
- 239000000835 fiber Substances 0.000 description 4
- 238000010166 immunofluorescence Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 230000000451 tissue damage Effects 0.000 description 4
- 231100000827 tissue damage Toxicity 0.000 description 4
- 102000015775 Core Binding Factor Alpha 1 Subunit Human genes 0.000 description 3
- 108010024682 Core Binding Factor Alpha 1 Subunit Proteins 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 208000035896 Twin-reversed arterial perfusion sequence Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 3
- 239000012531 culture fluid Substances 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000035876 healing Effects 0.000 description 3
- 238000011532 immunohistochemical staining Methods 0.000 description 3
- 208000028867 ischemia Diseases 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 230000002980 postoperative effect Effects 0.000 description 3
- 230000001172 regenerating effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 102400000888 Cholecystokinin-8 Human genes 0.000 description 2
- 101800005151 Cholecystokinin-8 Proteins 0.000 description 2
- 101000908391 Homo sapiens Dipeptidyl peptidase 4 Proteins 0.000 description 2
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102000004067 Osteocalcin Human genes 0.000 description 2
- 102100031475 Osteocalcin Human genes 0.000 description 2
- 108090000573 Osteocalcin Proteins 0.000 description 2
- 102000003982 Parathyroid hormone Human genes 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000004520 agglutination Effects 0.000 description 2
- RGCKGOZRHPZPFP-UHFFFAOYSA-N alizarin Chemical compound C1=CC=C2C(=O)C3=C(O)C(O)=CC=C3C(=O)C2=C1 RGCKGOZRHPZPFP-UHFFFAOYSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000002975 chemoattractant Substances 0.000 description 2
- 239000005482 chemotactic factor Substances 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 230000006020 chronic inflammation Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 230000004072 osteoblast differentiation Effects 0.000 description 2
- 239000000199 parathyroid hormone Substances 0.000 description 2
- 229960001319 parathyroid hormone Drugs 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108010048734 sclerotin Proteins 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 208000010392 Bone Fractures Diseases 0.000 description 1
- 108010008951 Chemokine CXCL12 Proteins 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 108010061414 Hepatocyte Nuclear Factor 1-beta Proteins 0.000 description 1
- 102100022123 Hepatocyte nuclear factor 1-beta Human genes 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000016921 Integrin-Binding Sialoprotein Human genes 0.000 description 1
- 108010028750 Integrin-Binding Sialoprotein Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 102100025368 Runt-related transcription factor 2 Human genes 0.000 description 1
- 101710102802 Runt-related transcription factor 2 Proteins 0.000 description 1
- 101150086605 Runx2 gene Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 102000007591 Tartrate-Resistant Acid Phosphatase Human genes 0.000 description 1
- 108010032050 Tartrate-Resistant Acid Phosphatase Proteins 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004763 bicuspid Anatomy 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000004097 bone metabolism Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000010609 cell counting kit-8 assay Methods 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000006041 cell recruitment Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 210000003725 endotheliocyte Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 238000000556 factor analysis Methods 0.000 description 1
- 210000004195 gingiva Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000009940 knitting Methods 0.000 description 1
- 239000012939 laminating adhesive Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000010232 migration assay Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 230000001582 osteoblastic effect Effects 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 210000004261 periodontium Anatomy 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000007447 staining method Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000004406 stave cell Anatomy 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/29—Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/195—Chemokines, e.g. RANTES
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses application of PTH combining SDF-1 in preparing medicine for improving periodontal tissue regeneration. A medicinal form of the SDF-1 is a medical collagen repairing film containing the SDF-1. Stem cells can be regulated to differentiate in the osteogenesis direction by jointly using the medical collagen repairing film containing the SDF-1 and the PTH to guide formation of new periodontal attachment. The medical collagen repairing film containing the SDF-1 is excellent in physical property, good in flexibility, degradable in a body and good in biocompatibility; a porous net-shaped three-dimensional structure of the medical collagen repairing film can continuously maintain an isolating barrier effect of a tissue, can provide space for the collected stem cells and facilitates attachment, proliferation and differentiation of the stem cells.
Description
Technical field
The present invention relates to PTH associating SDF-1 application in preparation promotes the medicine of paradenlal tissue regeneration.
Background technology
Periodontal disease causes alveolar bone to destroy absorption, and Periodontal Supporting Tissue lacks, and is the main cause causing loss of tooth.Tooth
The main target of week sick treatment is to obtain the regeneration of periodontal tissue.The effect of paradenlal tissue regeneration treatment is largely dependent upon
The quality and quantity of the periodontal regenerative sexual cell of disease damage Local residues, yet with the impact of long-term chronic inflammation, lesional area tooth
All lazy weights of regenerative cell, function are the best.How to obtain the key that enough periodontal regenerative sexual cells are periodontal disease therapeutics.
In recent years, tissue engineering technique becomes the focus of research.But it is translated into clinical practice to remain at many obstacles.
Stroma cell derivative factor-l (Stromal cell derived factor-1, SDF-1) is a kind of important cell chemotactic factor,
In the existing numerous researchs of medical science other field.CXCR4 (C-X-C chemokine receptor type 4) is the receptor of SDF-1,
Being expressed in multiple ancestral cells surface, can couple mediation it migrates with SDF-1.Impaired mouse brain, heart, muscle,
During liver, kidney, skin and knitting, the rising of damaged part SDF-1 can as potential chemoattractant, raise blood circulation or
Stem cell/the precursor of local expression CXCR4, produces tissue-specific differentiation to repair wound.SDF-1 is to periodontal membrane
Stem cell has chemotactic and promotees the effect of proliferation and differentiation, and topical application SDF-1 can remarkably promote mescenchymal stem cell and hematopoietic stem cell
Going back to the nest to periodontal and create district, promote angiogenesis, reduce inflammation reaction, increases new bone volume and density, strengthens area of new bone quality,
It it is a kind of chemoattractant in original position organizational project with application prospect.But, its action effective is affected by DPP-IV/CD26.
CD26 is II type transmembrane glycoprotein, and the many hematopoietic cells such as T activated and bone-marrow-derived lymphocyte, capillary endotheliocyte, epithelium is thin
Born of the same parents and stem cell are expressed DPP-IV, DPP-IV and are also present in blood plasma with soluble active.DPP-IV can crack and include
SDF-1 is at interior many chemotactic factors, somatomedin, nerve polypeptide and other important polypeptide.Therefore, searching can suppress
The preparation of SDF-1 degraded, for improving the activity of SDF-1, promotes that tissue regeneration effect has great importance.
Parathyroid hormone (parathyroid hormone, PTH) is unique dredging for treating sclerotin through U.S. FDA approval
The bone anabolism medicine of pine, its level raises can promote bone metabolism.Vivo and vitro experiment all proves that intermittent application PTH is to bone
Anabolism has facilitation.At cellular level, batch applications PTH can promote that bone stave cell is divided into osteoblast, makes
Osteoblastic quantity increases.In tissue level, as intermittence application PTH, PTH can promote the anabolism of bone, performance
Area, density and intensity for bone increase.PTH also has stem cell mobilization effect, and research shows that PTH can effectively mobilize
Marrow stromal cell enters blood.Ischemia (damage) can excite the depression effect to DPP-IV that PTH mediates, thus on
Adjust the level of SDF-1, thus be conducive to raising CXCR4+ cell and move cell from bone marrow through blood flow migrates to ischemic tissue.
The precursor that intermittent application PTH can be effectively facilitated mice is mobilized.
But, by regulation and control SDF-1/CXCR4 axle, current PTH promotes that heart and injury side is more of concentrated in the research of tissue regeneration
Face, the research being applied to other tissue injurys is the fewest, if the damage academia being adapted to its hetero-organization there is no unified viewpoint.
Not being both with heart ischemia damage, periodontal disease is a kind of chronic infectious disease, due to the chronic inflammation that periodontal lesional area is long-term
Disease causes the hard and soft tissue including gingiva, periodontal membrane, alveolar bone and cementum to damage, its pathogenesis and cure mechanism with
Heart ischemia damage is entirely different, and therefore can PTH Yu SDF-1 be combined and be used for the regeneration of periodontal tissue and have and greatly can not
Expection property, and be not currently also related to PTH associating SDF-1 and treat the report of periodontal tissue's damage.
Summary of the invention
For above-mentioned prior art, it is an object of the invention to provide PTH associating SDF-1 and promote paradenlal tissue regeneration in preparation
Application in medicine.
For achieving the above object, the present invention uses following technical proposals:
A first aspect of the present invention, it is provided that PTH associating SDF-1 application in preparation promotes the medicine of paradenlal tissue regeneration.
In above-mentioned application, the medicinal forms of described SDF-1 is the medical collagen repair membrane containing SDF-1.
In above-mentioned application, in the described medical collagen repair membrane containing SDF-1, the content of SDF-1 is that 5-8 μ g/ opens；It is preferably
5 μ g/ open.
A second aspect of the present invention, it is provided that a kind of medicine treating periodontal disease, comprises PTH and SDF-1, PTH and SDF-1
Weight ratio be 1:3-5.It is preferably 1:4.
Although it should be noted that the report of the most existing PTH associating SDF-1 treatment heart and injury, but there is no the two combination and promote
Enter the research report of paradenlal tissue regeneration.Owing to the site of tissue damage of human body has multiple, the cell regeneration energy of different damage locations
Power also significant difference, therefore, treatment thoughts and medicine for different tissues damage location are the most varied, different tissues
Portability is not had between the medicine of damage.So the drug combination of the present invention possesses unobviousness.The present invention will
PTH associating SDF-1 is for the treatment of periodontal tissue's damage, it is possible to produce the collaborative effect promoting tissue regeneration.External internal
It is demonstrated experimentally that PTH associating SDF-1 has extraordinary therapeutic effect to periodontal tissue's damage.
Beneficial effects of the present invention:
The present invention is combined with PTH by the medical collagen repair membrane containing SDF-1, it is possible to stem cell breaks up to skeletonization direction in regulation and control,
Guide the formation of new-attachment of periodontium.Wherein, the good physical properties of the medical collagen repair membrane containing SDF-1, pliability is good,
Can degradation in vivo, good biocompatibility, the three dimensional structure of its holey can not only persistently maintain the isolation barrier effect of tissue,
Space, beneficially stem cell can also be provided to adhere to for the stem cell raised, breed and differentiation.The present invention uses medical collagen to repair
Laminating adhesive is that carrier carries SDF-1, it is possible to promotes the stem cell recruitment effect of SDF-1, provides attachment site for cell, is conducive to
It is created district's field planting at periodontal, breeds and differentiation.Meanwhile, the combination of medical collagen repair membrane and SDF-1 also can reduce SDF-1 and exists
The loss in paradental defect district and volatilization, make defect local maintain higher drug level and slowly discharge, thus effectively play pharmacology
Effect.
Accompanying drawing explanation
Fig. 1: PTH combines promotion Periodontal ligament stem cell with SDF-1 breeds and migration results；
The impact that periodontal ligament stem cell alkaline phosphatase activities and Mineral nodules are formed by Fig. 2: PTH and SDF-1 use in conjunction；
Fig. 3: PTH and SDF-1 use in conjunction is on periodontal ligament stem cell BSP, the impact of OCN and Runx2 gene expression；
Fig. 4: PTH combines the recruitment to rat periodontal ligament defective region CXCR4+ cell with SDF-1；
Fig. 5: PTH combines with SDF-1 rat periodontal ligament defective region MSCs is raised effect；
Ge Zu paradental defect district periodontal osteanagenesis situation is compared in Fig. 6: postoperative different times H&E dyeing；
Cementum, periodontal membrane fiber regeneration situation are respectively organized in Fig. 7: healing later stage H&E dyeing；
Fig. 8: paradental defect district skeletonization associated protein immunohistochemical staining and TRAP dyeing.
Detailed description of the invention
The present invention is further illustrated in conjunction with the embodiments, it should explanation, the description below merely to explain the present invention,
Its content is not defined.
Embodiment 1:PTH is studied with the united experiment in vitro of SDF-1
1. experimental technique:
Separate from the healthy premolars pulled out because correction needs, cultivate Periodontal ligament stem cell (human periodontal
Ligament stem cells, hPDLSCs), screen single cell clone with limiting dilution assay；In experiment in vitro, the application of SDF-1 is dense
Degree is 50ng/ml for the application concentration of 200ng/ml, PTH, and PTH is intermittent application.Experiment is divided into four groups: A group for the moon
Property matched group, without PTH and SDF-1；B group PTH Han 50ng/ml；C group SDF-1 Han 200ng/ml；D group contains 50ng/ml
PTH and 200ng/ml SDF-1.In B group and D group, PTH is intermittent application, i.e. in the cultivation cycle of every 48h,
At initial 6h, cell adds the culture fluid containing 50ng/ml PTH.After cell is exposed to PTH 6h, changing liquid, cell exists
Without being further cultured for 42h in the culture fluid of PTH, every 48h changes a culture fluid.
(1) by cell viability detection kit (cell-counting kit-8, CCK8), cell migration assay detection PTH with
SDF-1 combines the impact migrating periodontal ligament stem cell and breeding.
(2) gathered by alkali phosphatase (Alkaline phosphatase, ALP) active testing, Alizarin red staining method and real-time quantitative
Synthase chain reaction (quantitative real-time polymerase chain reaction, qRT-PCR) measures PTH with SDF-1 and combines
The application impact on hPDLSCs Osteoblast Differentiation ability.
(3) use SPSS16.0 statistical analysis software to carry out statistical analysis, relevant parameter used one factor analysis of variance,
Data all represent with meansigma methods ± standard error (Mean ± SEM).< when 0.05, difference has statistical significance to P.
2. experimental result:
(1) being successfully separated and turn out Periodontal ligament stem cell, cellular morphology is normal, in good condition.
(2) PTH Yu SDF-1 use in conjunction can promote propagation and the transfer ability of PDLSCs: CCK8 result shows PTH
Promote that with SDF-1 use in conjunction the effect of cell proliferation is the strongest (P < 0.05) (A in Fig. 1)；Migrate experiment and show that experimental group all can
Promote the migration (P<0.05) of periodontal ligament stem cell, after associating PTH, make rush migration effect higher (P>0.05) (Fig. 1 of SDF-1
Middle B-C).
(3) PTH Yu SDF-1 use in conjunction can promote the Osteoblast Differentiation of PDLSCs: ALP active testing result is cell
When cultivating 7 days, PTH and SDF-1 use in conjunction can dramatically increase ALP activity (P < 0.05), experiment when cell is cultivated 14 days
ALP activity between group and matched group there was no significant difference (P > 0.05), shows that PTH Yu SDF-1 use in conjunction is trained at cell
The early stage supported can increase ALP activity (A in Fig. 2)；Alizarin red staining result shows that PTH with SDF-1 use in conjunction can be notable
Promote the formation (P < 0.05) (B-C in Fig. 2) of Mineral nodules；QRT-PCR result display PTH Yu SDF-1 use in conjunction can
Raise skeletonization Research of predicting markers resorption lacunae (bone sialoprotein, BSP), Runt associated transcription factor 2 (runt related
Transcription factor 2, Runx2), the gene expression dose (P < 0.05) (Fig. 3) of Bone Gla protein (osteocalcin, OCN).
Embodiment 2:PTH is studied with the united experiment in vivo of SDF-1
1. experimental technique:
Select 60 male Wistar rats (8 week old, 220～250g), by number of animals, be randomly divided into two big groups, often group
Lumbar injection PTH (the 40 μ g/kg) next day of 30: one group, another organizes lumbar injection normal saline.All rats are cooked bilateral
Mandibular bone is windowed defect, places the collagem membrane containing SDF-1 (5 μ g) in the defect of left side, and the collagem membrane containing PBS is placed on right side.This reality
Test and be divided into 4 groups: only at the matched group of the blank collagem membrane of defect local placement, local applying SDF-1 group, lumbar injection PTH group,
Local applies SDF-1 lumbar injection PTH group simultaneously.Take 3 days, 1 week, 2 weeks, 4 weeks, 8 weeks when collecting as Postoperative Specimen
Between point, often group takes 6 samples in each time.Fixing rear conventional EDTA decalcification in 4% paraformaldehyde after sampling, dehydration,
Transparent, paraffin embedding, prepare paraffin section.
Preparation method containing SDF-1 medical collagen repair membrane is: with PBS, the SDF-1 of powder being made into concentration is
The solution of 50 μ g/ml, is placed in medical collagen repair membrane in SDF-1 solution, finally soaked collagem membrane is placed on 6 orifice plates
In, place 12h for 4 DEG C and make it fully absorb liquid.SDF-1 and collagem membrane with magnitude relation: 5 μ g/ open.
(1) CXCR4 immunofluorescence dyeing and the double dye of CD34-/CD90+ immunofluorescence is used to observe paradental defect agglutination
Middle PTH with SDF-1 combines the impact of the expression on SDF-1 receptor CXCR 4 and to mescenchymal stem cell (mesenchymal
Stem cells, MSCs) raise situation.
(2) HE dyeing detection paradental defect district periodontal membrane, cementum, the regeneration situation of alveolar bone.
(3) row ALP, Runx2, type i collagen (collagen, Col I) immunohistochemical staining, and carry out anti-tartaic acid phosphorus
Acid enzyme (Tartrate-resistant acid phosphatase, TRAP) dyeing, compares defective region skeletonization in four groups of agglutinations anti-with broken bone
The difference answered.
(4) the data obtained all represents with mean ± standard deviation.Application SPSS16.0 statistical package, carries out list to relevant parameter
Analysis of variance, < when 0.05, difference has statistical significance to P.
2. experimental result:
(1) postoperative laboratory animal all survives, and occurs without obvious inflammation and immunological rejection at defect.By to paraffin section
CXCR4 immunofluorescence dyeing and the double dye of CD90+/CD34-immunofluorescence, result shows, each time point PTH with
CXCR4+ cell and MSCs that SDF-1 associating is raised are all many compared with other groups, difference statistically significant (P < 0.05) (Fig. 4,
5)。
(2) paradental defect district H&E coloration result shows, PTH with SDF-1 combines can promote to create district's skeletonization in early days, and formed
Level of Alveolar Bone pulp cavity is less, eburnation, and area of new bone area is higher than other each group and has significant difference (P < 0.05) (Fig. 6).Tooth
All membrane fibers and cementum new life occur in healing later stage (4,8 weeks), and PTH+SDF-1 group neonatal tooth sclerotin goes out at the 4th Zhou Shiyi
Existing, to the most relatively other group thickness when the 8th week.By by each group of new life fiber angles compared with natural periodontal membrane angle (47.202 °),
Find that the newborn periodontal membrane fiber angle (50.289 °) the 8th week PTH+SDF-1 group is most bordering on natural teeth week film (Fig. 7).
(3) skeletonization associated protein immunohistochemical staining result shows, PTH with SDF-1 combines can promote that paradental defect heals
Commitment ALP and Runx2 expresses, and has significant difference (P < 0.05) with other each group.Phase after healing, PTH+SDF-1 group
Col I expression is higher, and SDF-1 group no significant difference (P > 0.05), but higher than PTH group and matched group, difference has statistics to anticipate
Justice (P < 0.05).TRAP coloration result shows, PTH with SDF-1 combines can activate osteoclast generation in early days, promotes the conjunction of bone
Become metabolism (Fig. 8).
Although the detailed description of the invention of the present invention is described by the above-mentioned accompanying drawing that combines, but not limit to scope
System, one of ordinary skill in the art should be understood that on the basis of technical scheme, and those skilled in the art need not pay
Go out various amendments or deformation that creative work can make still within protection scope of the present invention.
Claims (7)
1.PTH associating SDF-1 application in preparation promotes the medicine of paradenlal tissue regeneration.
Apply the most as claimed in claim 1, it is characterised in that the medicinal forms of described SDF-1 is medical containing SDF-1
Collagen repair membrane.
Apply the most as claimed in claim 2, it is characterised in that in the described medical collagen repair membrane containing SDF-1, SDF-1
Content be that 5-8 μ g/ opens.
Apply the most as claimed in claim 3, it is characterised in that in the described medical collagen repair membrane containing SDF-1, SDF-1
Content be that 5 μ g/ open.
5. treating a medicine for periodontal disease, the weight ratio comprising PTH and SDF-1, PTH and SDF-1 is 1:3-5.
6. medicine as claimed in claim 5, it is characterised in that the weight ratio of PTH Yu SDF-1 is 1:4.
7. comprise the clinical preparation of medicine described in claim 5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610252121.4A CN105797139A (en) | 2016-04-21 | 2016-04-21 | Application of PTH combining SDF-1 in preparing medicine for improving periodontal tissue regeneration |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610252121.4A CN105797139A (en) | 2016-04-21 | 2016-04-21 | Application of PTH combining SDF-1 in preparing medicine for improving periodontal tissue regeneration |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105797139A true CN105797139A (en) | 2016-07-27 |
Family
ID=56458316
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610252121.4A Pending CN105797139A (en) | 2016-04-21 | 2016-04-21 | Application of PTH combining SDF-1 in preparing medicine for improving periodontal tissue regeneration |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105797139A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112220967A (en) * | 2020-11-26 | 2021-01-15 | 山东大学 | Targeting antibacterial and in-situ bone-promoting dual-functional material and preparation method and application thereof |
-
2016
- 2016-04-21 CN CN201610252121.4A patent/CN105797139A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| Y. JUNG等: "Regulation of SDF-1 (CXCL12) production by osteoblasts; a possible mechanism for stem cell homing", 《BONE》 * |
| 葛少华等: "PTH和SDF-1联合应用对牙周膜干细胞生物学活性及牙周组织再生的影响", 《2016牙周病学学术研讨会论文集》 * |
| 褚云娟: "基质细胞衍生因子-1（SDF-1)与牙周组织自体（原位）再生", 《口腔医学研究》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112220967A (en) * | 2020-11-26 | 2021-01-15 | 山东大学 | Targeting antibacterial and in-situ bone-promoting dual-functional material and preparation method and application thereof |
| CN112220967B (en) * | 2020-11-26 | 2021-08-03 | 山东大学 | Targeting antibacterial and in-situ bone-promoting dual-functional material and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Qiu et al. | Enhancement of periodontal tissue regeneration by conditioned media from gingiva-derived or periodontal ligament-derived mesenchymal stem cells: a comparative study in rats | |
| Liu et al. | Local administration of stromal cell-derived factor-1 promotes stem cell recruitment and bone regeneration in a rat periodontal bone defect model | |
| Miyahara et al. | Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction | |
| Flores et al. | Cementum–periodontal ligament complex regeneration using the cell sheet technique | |
| Cao et al. | Adenovirus-mediated transfer of hepatocyte growth factor gene to human dental pulp stem cells under good manufacturing practice improves their potential for periodontal regeneration in swine | |
| Yu et al. | Human gingiva-derived mesenchymal stromal cells contribute to periodontal regeneration in beagle dogs | |
| Osugi et al. | Conditioned media from mesenchymal stem cells enhanced bone regeneration in rat calvarial bone defects | |
| Grzesik et al. | Cementum and periodontal wound healing and regeneration | |
| CN104324053B (en) | A kind of dog stem cell secretion factor reparation liquid of quick healing dog wound tissue | |
| CN104225681A (en) | Tissue-engineered bone and preparation method thereof | |
| Yu et al. | Effects of short-term inflammatory and/or hypoxic pretreatments on periodontal ligament stem cells: in vitro and in vivo studies | |
| CN103585177A (en) | Applications of mesenchymal stem cell and genetically modified mesenchymal stem cell | |
| Zhu et al. | Applications of mesenchymal stem cells in liver fibrosis: novel strategies, mechanisms, and clinical practice | |
| CN105013014A (en) | Preparation method and application of acellular matrix biological material | |
| CN105255824A (en) | Periodontal ligament stem cell osteogenic differentiation inducing liquid and method | |
| Sándor et al. | Combining adipose-derived stem cells, resorbable scaffolds and growth factors: An overview of tissue engineering | |
| Dziedzic et al. | Adipose-derived stromal cells and mineralized extracellular matrix delivery by a human decellularized amniotic membrane in periodontal tissue engineering | |
| CN105797139A (en) | Application of PTH combining SDF-1 in preparing medicine for improving periodontal tissue regeneration | |
| CN103387959A (en) | Stem cell from deciduous teeth, and preparation method and application thereof | |
| CN103736150A (en) | Application of melatonin synergistic extracellular matrix biomaterial to preparation of medicament for promoting osteoblast differentiation of mesenchymal stem cells | |
| Feng et al. | Periodontal ligament‐like tissue regeneration with drilled porous decalcified dentin matrix sheet composite | |
| CN101182493A (en) | Transgenic mesenchyma stem cell for curing radiation enteritis and method of producing the same | |
| Bi et al. | Hertwig's epithelial root sheath cells show potential for periodontal complex regeneration | |
| CN105326864A (en) | Stem cell-based preparation for treating systemic lupus erythematosus and preparation method thereof | |
| Khan et al. | Salivary gland tissue engineering to attain clinical benefits: a special report |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160727 |
|
| RJ01 | Rejection of invention patent application after publication |