CN107137711A - Application of the albumen of Kindlin 2 as target spot in the medicine for treating Osteoarthritis is prepared - Google Patents
Application of the albumen of Kindlin 2 as target spot in the medicine for treating Osteoarthritis is prepared Download PDFInfo
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- CN107137711A CN107137711A CN201710170718.9A CN201710170718A CN107137711A CN 107137711 A CN107137711 A CN 107137711A CN 201710170718 A CN201710170718 A CN 201710170718A CN 107137711 A CN107137711 A CN 107137711A
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- kindlin
- albumen
- medicine
- osteoarthritis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/0008—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
- A61K48/0025—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/10—Musculoskeletal or connective tissue disorders
- G01N2800/101—Diffuse connective tissue disease, e.g. Sjögren, Wegener's granulomatosis
- G01N2800/102—Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints
Abstract
A kind of application the present invention relates to albumen of Kindlin 2 as target spot in the medicine for treating Osteoarthritis is prepared.Through result of study, after the Gene-specific knockouts of Kindlin 2, the articular cartilage of mouse and subchondral bone heavy damage, articular cartilage area are substantially reduced, and arthroncus is serious, and the pain threshold of mouse is remarkably decreased.Experimental result prompting Kindlin 2 albumen of this research can as the medicine for treating Osteoarthritis a novel targets.
Description
Technical field
The present invention relates to drug field, more particularly to a kind of Kindlin-2 albumen is preparing treatment bone as target spot
Application in arthritic medicine.
Background technology
Osteoarthritis is a kind of degenerative arthritis disease, generally occurs in mid-aged population, often shows as cartilage
The symptoms such as lower curing, chronic synovitis, periarticular osteophyte formation.As China enters aging society, Osteoarthritis
Patient groups are rising with surprising rapidity, and Osteoarthritis easily causes pain, walking disorder etc., has a strong impact on patient's
Quality of life.The treatment of current Osteoarthritis mainly includes the schemes such as motion, joint care, medicine pain relief.But this
A little schemes are often cured the symptoms, not the disease, it is impossible to Osteoarthritis is treated from root, the medicine used often lack of targeted and spy
The opposite sex, therefore, very exigence researches and develops new specific treatment medicine for treating arthritis.
The content of the invention
Based on this, it is necessary to provide a kind of Kindlin-2 albumen as target spot and preparing the medicine for the treatment of Osteoarthritis
In application.
Application of the Kindlin-2 albumen in the medicine for preparing treatment Osteoarthritis, the drug targeting Kindlin-
2 albumen, the medicine can promote Kindlin-2 GFPs to transcribe or express.
In one embodiment, the Kindlin-2 albumen in the drug targeting cartilage cell.
In one embodiment, the medicine can improve the expression quantity of Kindlin-2 albumen in cartilage cell
The expression quantity of Kindlin-2 albumen.
Rush is included in a kind of medicine for treating Osteoarthritis, the drug targeting Kindlin-2 albumen, the medicine
Enter the composition of the transcription of Kindlin-2 GFPs or expression.
In one embodiment, the Kindlin-2 albumen in the drug targeting cartilage cell.
In one embodiment, the medicine can improve the expression quantity of the Kindlin-2 albumen in cartilage cell.
A kind of pharmaceutical composition for treating Osteoarthritis, including Kindlin-2 albumen accelerator and targeting agent, institute
State Kindlin-2 albumen accelerator to be carried in the targeting agent, the targeting agent targets Kindlin-2 albumen.
In one embodiment, the targeting agent in AAV viruses, miRNA and polymer micelle at least one
Kind.
In one embodiment, Kindlin-2 albumen accelerator is the gene of expressing K indlin-2 albumen, described
Targeting agent is AAV viruses, and the gene of the albumen of the expressing K indlin-2 is carried in the AAV viruses.
Kindlin-2 albumen prepare Osteoarthritis detection reagent in application, the detection reagent with
Kindlin-2 albumen as Osteoarthritis biomarker.
Test result indicates that, after Kindlin-2 Gene-specific knockouts, the articular cartilage and subchondral bone of mouse are tight
Destroy again, articular cartilage area is substantially reduced, arthroncus is serious, and the pain threshold of mouse is remarkably decreased.The experiment of this research
As a result prompting Kindlin-2 albumen can as the medicine for treating Osteoarthritis a novel targets.
Brief description of the drawings
Fig. 1 is the result figure after the articular cartilage ABG dyeing of experimental group and control group mice in embodiment 1；
Fig. 2 is that the articular cartilage of experimental group and control group mice in embodiment 1 is surveyed using Image Pro plus7 softwares
Measure the statistical results chart of the area of articular cartilage in shin bone and femur；
Fig. 3 is experimental group and the control group mice Bones and joints model that 3D is reconstructed after minitype CT scanning analysis in embodiment 2
Figure；
Fig. 4 is experimental group and the kneed outside drawing of control group mice in embodiment 3；
Fig. 5 is the pain threshold statistical result of experimental group and control group mice in embodiment 4.
Embodiment
In order to facilitate the understanding of the purposes, features and advantages of the present invention, with reference to specific embodiment and
Accompanying drawing is described in detail to the embodiment of the present invention.Elaborate in the following description many details so as to
In fully understanding the present invention.But the invention can be embodied in many other ways as described herein, this area skill
Art personnel can do similar improvement in the case of without prejudice to intension of the present invention, therefore the present invention is not by following public specific
The limitation of implementation.
Application of the Kindlin-2 albumen of one embodiment in the medicine for preparing treatment Osteoarthritis, wherein, should
Drug targeting Kindlin-2 albumen, the medicine can promote Kindlin-2 GFPs to transcribe or express.
Kindlin-2 albumen is a kind of vinculin, may participate in the activation of integrin, and there are some researches show it is in muscle
Played an important role in the extension of cell.But it is less as the research of target treatment on Kindlin-2 albumen, at present still
Have no its research report in terms of Osteoarthritis.And the present inventor has been surprisingly found that after experimental study
There is close correlation with Osteoarthritis in the expression of Kindlin-2 albumen.It is small after Kindlin-2 Gene-specific knockouts
The articular cartilage of mouse and subchondral bone heavy damage, articular cartilage area are substantially reduced, and arthroncus is serious, the pain of mouse
Threshold value is remarkably decreased.The experimental result of this research provides a new target spot to treat the medicine of Osteoarthritis.Medicine leads to
Targeting Kindlin-2 albumen is crossed, promotes the transcription of Kindlin-2 GFPs or expresses, assist Osteoarthritis treatment.
Specifically, described " medicine for the treatment of Osteoarthritis " can be diagnosed as bone for treatment herein
The medicine of arthritic patient's preparation or the medicine prepared for prevention Osteoarthritis.
An embodiment Kindlin-2 albumen prepare treatment Osteoarthritis medicine in application in, should
Kindlin-2 albumen in drug targeting cartilage cell.Cartilage cell and Osteoarthritis have it is close associate, pass through medicine
Kindlin-2 albumen in thing targeting cartilage cell, can further strengthen the specificity of medicine, reduce side effect.
In one embodiment, the medicine is specially and can target Aggrecan (the poly- enzyme of collectin) to be positive
Cell.
An embodiment Kindlin-2 albumen prepare treatment Osteoarthritis medicine in application in, should
Medicine can improve the expression quantity of Kindlin-2 albumen in cartilage cell.Result of study shows, Kindlin-2 gene specifics
Mouse articular cartilage area after knockout is substantially reduced, point out when Kindlin-2 protein secretions are reduced, articular cartilage by
Damage, further cause the symptoms such as Osteoarthritis.Therefore Kindlin-2 albumen can be used as treatment medicine for treating arthritis
One new target spot, can improve the expression quantity of Kindlin-2 albumen, specific Saving cortilage cartilage cell, prevention by medicine
Damaged articular cartilage.
More specifically, an embodiment Kindlin-2 albumen prepare treatment Osteoarthritis medicine in
In, the medicine can improve the expression quantity of Kindlin-2 albumen in articular chondrocytes.
To sum up, result of study shows, expression quantity and the Osteoarthritis of Kindlin-2 albumen have close correlation.
One novel targets of the medicine that Kindlin-2 albumen can treat Osteoarthritis as preparing, are preparing prevention or treatment bone
Had a good application prospect in the arthritic medicine of property.
In addition, the application also provides the medicine of the treatment Osteoarthritis of an embodiment, wherein, the drug targeting
The composition for promoting the transcription of Kindlin-2 GFPs or expression is included in Kindlin-2 albumen, the medicine.
Kindlin-2 albumen can be improved by promoting the composition of the transcription of Kindlin-2 GFPs or expression in the medicine
Expression quantity, specific Saving cortilage cartilage cell prevents damaged articular cartilage.
In one embodiment, the Kindlin-2 eggs in the drug targeting cartilage cell of the treatment Osteoarthritis
In vain.Further, the medicine can improve the expression quantity of the Kindlin-2 albumen in cartilage cell.
More specifically, cartilage cell can be articular chondrocytes, the drug targeting joint of the treatment Osteoarthritis is soft
Kindlin-2 albumen in osteocyte, and improve the expression quantity of the Kindlin-2 albumen in articular chondrocytes.
Said medicine using Kindlin-2 albumen as therapy target, by promote Kindlin-2 GFPs transcribe or
Expression is so as to treat Osteoarthritis.Result of study is shown, after Kindlin-2 Gene-specific knockouts, Kindlin-2 eggs
White expression quantity declines, and the articular cartilage of mouse and subchondral bone heavy damage, articular cartilage area are substantially reduced, arthroncus
Seriously, the pain threshold of mouse is remarkably decreased.Therefore by medicine Kindlin-2 GFPs can be promoted to transcribe or express, from
And treat Osteoarthritis.
Further, the application also provides the pharmaceutical composition that an embodiment treats Osteoarthritis, said composition bag
Kindlin-2 albumen accelerator and targeting agent are included, Kindlin-2 albumen accelerator is carried in targeting agent, targeting agent targeting
Kindlin-2 albumen.
Wherein, Kindlin-2 albumen accelerator is that can improve the medicine or reagent of Kindlin-2 expressing quantities, target
It is that can target Kindlin-2 albumen to agent.Kindlin-2 albumen accelerator can pass through the things such as chemical bond connection or cladding
Reason mode is carried in targeting agent.
In one embodiment, targeting agent can (Adeno-associated virus, gland be related selected from AAV viruses
Virus), at least one of miRNA (MicroRNA) and polymer micelle.
Specifically, AAV is viral, miRNA or polymer micelle as carrier by Kindlin-2 albumen accelerator carry to
Internal specific position, the release of Kindlin-2 albumen accelerator promotes the expression of internal Kindlin-2 albumen, so as to improve
The expression quantity of Kindlin-2 albumen, is repaired or Saving cortilage cartilage, so as to treat or prevent Osteoarthritis.
In one embodiment, Kindlin-2 albumen accelerator is the gene of expressing K indlin-2 albumen, targeting
Agent is AAV viruses, and the gene of expressing K indlin-2 albumen is carried in AAV viruses, and AAV cell entries body is interior and expresses
Kindlin-2 albumen, so as to improve the expression quantity of Kindlin-2 albumen.
The pharmaceutical composition of above-mentioned treatment Osteoarthritis, including Kindlin-2 albumen accelerator and targeting agent, two
Person acts synergistically, and improves the expression quantity of Kindlin-2 albumen, and then prevent or treatment Osteoarthritis.
In addition, the Kindlin-2 albumen that the application also provides an embodiment is preparing the detection reagent of Osteoarthritis
In application, wherein, biomarker of the detection reagent using Kindlin-2 albumen as Osteoarthritis.
Show that expression quantity and the Osteoarthritis of Kindlin-2 albumen have close correlation, therefore by research
Kindlin-2 albumen can as Osteoarthritis biomarker.Specifically, detection reagent can pass through Kindlin-2 eggs
White expression quantity judges the state of an illness of Osteoarthritis.
To sum up, have been surprisingly found that Kindlin-2 albumen has close correlation with Osteoarthritis after experimental study.
After Gene-specific knockout, Kindlin-2 expressing quantities decline, and cause the articular cartilage and subchondral bone of mouse seriously to be broken
Bad, articular cartilage area is substantially reduced, and arthroncus is serious, and the pain threshold of mouse is remarkably decreased.Experimental result is pointed out
Kindlin-2 albumen can be used as a novel targets for treating Osteoarthritis.Kindlin-2 albumen is preparing treatment bone
Had a good application prospect in the detection reagent of arthritic medicine or preparation Osteoarthritis.
It is specific embodiment below.
In embodiment using medicine and instrument if not otherwise indicated, it is this area conventional selection.It is unreceipted in embodiment
The experimental method of actual conditions, generally according to normal condition, such as condition or kit production described in document, books
The method of manufacturer's recommended is realized.
Not specified, WT represents wild type control mice in following examples, and cKO is represented using TAM induction
Mouse after the Kindlin-2 for the cartilage cell that specific knockdown Aggrecan is positive.Laboratory mice draws assorted big by the U.S.
Learn and provide, be male mouse.
Embodiment 1
Knock out the influence of Kindlin-2 gene pairs mouse articular cartilages
The experimental mice (cKO) at two monthly ages is subjected to TAM injection and knocks out Kindlin-2 to induce, he is not
The concentration of former times sweet smell is 10mg/ml, and the injection dosage to mouse is 0.1ml/10g body weight, five pins of continuous injection, a daily pin, one
A pin is mended after individual month again.Corn oil injection is carried out under experimental comparison group (WT) the same terms.Two months are spent, mouse is put to death, taken out
Knee joint, is fixed with formalin, then carries out decalcification 21 days with 10% EDTA, and with FFPE, section carries out ABG dyes
Color (Alcian blue andSafranin-O/fast green staining, alcian blue and sarranine/fast green dyeing), knot
Fruit is as shown in figure 1, compared to control group, in Aggrecan positive cells after specific knockdown Kindlin-2, articular cartilage and soft
Ostosis is badly damaged under bone.The area of in shin bone and femur articular cartilage is measured Fig. 1 with Image Pro plus7 softwares,
Statistical result is shown in Fig. 2.
Result above is shown, causes articular cartilage area in Aggrecan positive cells after specific knockdown Kindlin-2
Substantially reduce, point out the development of Kindlin-2 and Osteoarthritis to there is close contact.
Embodiment 2
The Kindlin-2 bases in Aggrecan positive cells are knocked out to experimental mice (cKO) as described in Example 1
Cause.Corn oil injection is carried out under experimental comparison group (WT) the same terms.Two months are spent, mouse is put to death, takes Bones and joints, use formaldehyde
It is fixed, minitype CT (μ CT) scanning analysis are carried out, then 3D is reconstructed, as a result as shown in figure 3, in Fig. 3, (a) figure represents that WT types are small
The front view of the Bones and joints of mouse, (b) figure represents the rearview of the Bones and joints of WT type mouse, and (c) figure represents the bone of cKO type mouse
The front view in joint, (d) figure represents the rearview of the Bones and joints of cKO type mouse.
In minitype CT (μ CT) scanning display Aggrecan positive cells after specific knockdown Kindlin-2, Bones and joints
Structure and form generation heavy damage.Prompting can by promote Kindlin-2 GFPs transcribe or expression chemoprophylaxis or
Treat Osteoarthritis.
Embodiment 3
The Kindlin-2 bases in Aggrecan positive cells are knocked out to experimental mice (cKO) as described in Example 1
Cause.Corn oil injection is carried out under experimental comparison group (WT) the same terms.Two months are spent, mouse is put to death, knee joint is taken out.Such as Fig. 4
Shown, in Aggrecan positive cells after specific knockdown Kindlin-2, mouse knee joint swelling is serious.
Embodiment 4
Behaviors survey measures pain index
The induction pain of mechanical force is determined according to the assay method of von Frey sensitiveness, von Frey tests are being carried out
Before, first test mice is allowed to be familiar with environment.When being measured, using a von Frey filament by calibration from below
The hind paw of mouse is stabbed, then according to iteration close to method, the power for calculating 50% retreats threshold value (force withdrawal
threshold).The pain threshold statistical result of experimental mice (cKO) and control group mice is as shown in Figure 5.Display
In Aggrecan positive cells after specific knockdown Kindlin-2, the pain threshold of mouse is remarkably decreased.
Embodiment described above only expresses the several embodiments of the present invention, and it describes more specific and detailed, but simultaneously
Can not therefore it be construed as limiting the scope of the patent.It should be pointed out that coming for one of ordinary skill in the art
Say, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to the guarantor of the present invention
Protect scope.Therefore, the protection domain of patent of the present invention should be determined by the appended claims.
Claims (10)
- Application of the 1.Kindlin-2 albumen in the medicine for preparing treatment Osteoarthritis, it is characterised in that the drug targeting Kindlin-2 albumen, the medicine can promote Kindlin-2 GFPs to transcribe or express.
- 2. application of the Kindlin-2 albumen according to claim 1 in the medicine for preparing treatment Osteoarthritis, it is special Levy and be, the Kindlin-2 albumen in the drug targeting cartilage cell.
- 3. application of the Kindlin-2 albumen according to claim 1 in the medicine for preparing treatment Osteoarthritis, it is special Levy and be, the medicine can improve the expression quantity of Kindlin-2 albumen in cartilage cell.
- 4. a kind of medicine for treating Osteoarthritis, it is characterised in that the drug targeting Kindlin-2 albumen, the medicine In include the composition for promoting the transcription of Kindlin-2 GFPs or expression.
- 5. the medicine for the treatment of Osteoarthritis according to claim 1, it is characterised in that the drug targeting cartilage cell In Kindlin-2 albumen.
- 6. the medicine for the treatment of Osteoarthritis according to claim 1, it is characterised in that the medicine can improve cartilage The expression quantity of Kindlin-2 albumen in cell.
- 7. a kind of pharmaceutical composition for treating Osteoarthritis, it is characterised in that including Kindlin-2 albumen accelerator and target To agent, the Kindlin-2 albumen accelerator is carried in the targeting agent, and the targeting agent targets Kindlin-2 albumen.
- 8. the pharmaceutical composition for the treatment of Osteoarthritis according to claim 7, it is characterised in that the targeting agent is selected from At least one of AAV viruses, miRNA and polymer micelle.
- 9. the pharmaceutical composition of the treatment Osteoarthritis according to claim 7 or 8, it is characterised in that described Kindlin-2 albumen accelerator is the gene of expressing K indlin-2 albumen, and the targeting agent is AAV viruses, the expression The gene of Kindlin-2 albumen is carried in the AAV viruses.
- Application of the 10.Kindlin-2 albumen in the detection reagent for preparing Osteoarthritis, it is characterised in that the detection examination Biomarker of the agent using Kindlin-2 albumen as Osteoarthritis.
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| CN201710170718.9A CN107137711B (en) | 2017-03-21 | 2017-03-21 | Application of Kindlin-2 protein as target in preparation of medicine for treating osteoarthritis |
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| CN201710170718.9A CN107137711B (en) | 2017-03-21 | 2017-03-21 | Application of Kindlin-2 protein as target in preparation of medicine for treating osteoarthritis |
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Cited By (2)
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| CN112843235A (en) * | 2021-01-27 | 2021-05-28 | 南方科技大学 | Application of reagent for inhibiting Kindlin-2 protein expression level in liver cells in preparation of fatty liver treatment product |
| CN115105597A (en) * | 2022-07-25 | 2022-09-27 | 南方科技大学 | Application of Kindlin-2 as target in treating osteoporosis and preventing cancer bone metastasis |
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| WO2012028703A1 (en) * | 2010-09-02 | 2012-03-08 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Method for the prognosis of the progression of cancer |
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| CN112843235A (en) * | 2021-01-27 | 2021-05-28 | 南方科技大学 | Application of reagent for inhibiting Kindlin-2 protein expression level in liver cells in preparation of fatty liver treatment product |
| CN115105597A (en) * | 2022-07-25 | 2022-09-27 | 南方科技大学 | Application of Kindlin-2 as target in treating osteoporosis and preventing cancer bone metastasis |
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| Publication number | Publication date |
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| CN107137711B (en) | 2020-07-31 |
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