CN107320726B - Application of the LncRNA-TUG1 in the drug that the stemness of preparation regulation periodontal ligament stem cell maintains ability - Google Patents
Application of the LncRNA-TUG1 in the drug that the stemness of preparation regulation periodontal ligament stem cell maintains ability Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- 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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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
- C12N2740/15041—Use of virus, viral particle or viral elements as a vector
- C12N2740/15043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
Abstract
The invention discloses application of the LncRNA-TUG1 in the drug that the stemness of preparation regulation periodontal ligament stem cell maintains ability.Present invention firstly discovers that LncRNA-TUG1 has played important regulating and controlling effect in periodontal ligament stem cell stemness maintenance process, when LncRNA-TUG1 is lowered, the proliferation of PDLSCs, self-renewing, differentiation, transfer ability are suppressed, thereby confirm that LncRNA-TUG1 can be used as the potential target spot of multipotential stem cell stemness maintenance, promotion is developed new about LncRNA-TUG1 related drugs or the factor, and regenerative medicine field is finally applied to, reach clinically really precisely medical treatment.
Description
Technical field
The present invention relates to oral tissue regeneration field technical fields, and in particular to LncRNA-TUG1 regulates and controls periodontal in preparation
The stemness of film stem cell maintains the application in the drug of ability.
Background technique
Paradenlal tissue regeneration is one of the emphasis of dentistry research, is Periodontics, maxillofacial surgery, correction, repairs
It the common objective of multidisciplinary area research such as goes back to school.In recent years, the progress about tooth steam cell and tissue engineering technique
New research direction is brought to the regeneration of periodontium biology.Seo in 2004 etc. utilizes single cell clone technology, from human body
It is successfully separated in periodontal membrane tissue and identifies a kind of new adult stem cell, i.e. periodontal ligament stem cell, carry out biology for oral cavity
New approaches have been opened up in function reparation.
Periodontal ligament stem cell (PDLSCs) is a kind of adult that acquisition, mesenchyma source are easier in clinical oral work
Stem cell；Be also one group of heterogeneous multipotential stem cell with multi-lineage potential, containing fibroblast, osteoblast, at
The various kinds of cell ingredient such as cement cell and undifferentiated precursor stem cell has the potential for synthesizing newborn periodontium, can migrate
It in diseased Root Surfaces and a series of biological actions such as migrated, be proliferated, break up, form newborn periodontium structure, established new
Attachment relationship plays extremely important leading role in periodontal regenerative.It can express stem cell labeling object and have stem cell
Sample characteristic (stem-cell-like ability), has self-renewing and Multidirectional Differentiation ability；It can show higher proliferation
And clonality, the Regeneration and Repair of periodontium can be maintained.In vitro by it is appropriate induction be capable of forming bone, cartilage,
The Various Tissues such as nerve, fat, blood vessel；Has the potential ability for being divided into osteoblast or cementoblast, and can be in body
Cementum-parodontium-alveolar bone spline structure object is formed after interior transplanting, regenerates that provide can for tooth and periodontium biology
Energy；In the bone tissue maintenance of clinical oral, osteanagenesis, periodontal remodeling, reparation and orthodontic treatment, PDLSCs can play differentiation,
The effects of proliferation, self-renewing, migration, to promote, Periodontium remodeling, biological root of the tooth are formed, bone tissue heals and osteanagenesis
Aspect provides important clinical value.Present inventor seminar takes the lead in proposing to utilize tooth early period in the world
Related stem cells carry out the new concept of biological dental root regeneration, and have carried out serial related In vitroandin vivotrial, such as in meiofauna
Successful regeneration goes out the biological root of the tooth that can normally function on model；The periodontal that self allosome periodontal ligament stem cell and Vc are induced
Film stem cell diaphragm is used for regeneration, and achieves good effect；Meanwhile finding that the expression for inhibiting miRNA-21 can promote
Into periodontal ligament stem cell Osteoblast Differentiation and regeneration.
In human genome research, scholars have found that a kind of length is more than non-coding RNA (the long non of 200bp
Coding RNA, lncRNA), this kind of RNA itself does not encode albumen, transcribed by eukaryotic gene group from, in the form of RNA
There are in a variety of levels, such as the expression of epigenetic regulation, transcriptional control and post-transcriptional control controlling gene.Research
It has been shown that, LncRNA participate in numerous life adjusting activities: can carry out epigenetics adjusting to protein coding gene；Directly adjust
Genetic transcription and protein degradation；Participate in certain organelles generating process and intracellular molecules subcellular transport, and often with
Gene imprinting phenomenon is related.
The expression product that taurine raises gene 1 (Taurine upregulated gene 1, TUG1) is a kind of long-chain
Non-coding RNA.It most early in being found in mouse retinal cells, expresses in nucleus and cytoplasm, can draw after knocking out TUG1
Retinal development deformity is played, cell decreased growth or apoptosis are caused.LncRNA-TUG1 is located at human chromosomal 22q12.2, length
About 7.1kb, has several open reading frames but longest coding is no more than 100 amino acid, therefore, it is considered that it is non-volume
Code RNA.It can with polycomb repressive complex 2 (PRC2) protein binding of methylation, to regulate and control certain
The expression of a little growth control genes.Silencing TUG1 can lead to cell decreased growth or apoptosis, several and apoptosis-related
Gene expression up-regulation after silencing TUG1.For retinal progenitor cells carry out TUG1siRNA transfection after three days, several and cell
The relevant gene expression up-regulation of apoptosis pathway, cell death increase, and the normal expression of TUG1 may be for inhibiting certain cells to wither
Related gene is died to play an important role.TUG1 has adjustment effect to SM22 α in vascular smooth muscle cells.After striking low TUG1, carefully
Intracellular growth slows down or apoptosis, SM22 α mRNA expression up-regulation；It can inhibit 2 (Polycomb of complex with more comb albumen
Repressive complex 2, PRC2) in EZH2 protein binding, thus regulate and control it is certain growth control genes expression；Endochylema
In EZH2 have methyl transferase activity and PDGF induction cell pseudopodium forming process in play a crucial role, obtain
Interaction mechanism between TUG1 and EZH2, F-actin and its adjustment effect to vascular smooth muscle cells skeleton.Study people
It includes some highly conserved P53 binding sites that member, which also found TUG1 promoter nearby, can be answered by the P53 DNA damage mediated
Answering stimulates and expresses up-regulation.
The stemness of stem cell maintains ability, be mainly reflected in high proliferation, low differentiation, self-renewing, have transfer ability and
The expression (stemness associated genes) of stemness related gene (such as Sox2, KLF4, Nanog, c-myc and oct4),
It is typically considered to that the stemness of stem cell can be maintained.Recent research have also shown that these main bodies of stem cell related gene expression
In present some tumours, and the tumor formation and transfer of modulate tumor, stemness related gene and its signal path may be tumour extremely
The mechanism for occurring and shifting.The promoter of silencing miR-302-367 cluster can make embryonic stem cell lack stem cell phenotype and
Characteristic, and cell has Pluripotent embryonic stem cells characteristic after being overexpressed miR-302-367 cluster in application on human skin cancer cell, performance
For the expression of stem cell labeling Oct3/4, SSEA-3, SSEA-4, Sox2 and Nanog.
However, not maintaining the report of ability about the stemness of LncRNA regulation Periodontal ligament stem cell also at present.
Summary of the invention
For the above-mentioned prior art, the object of the present invention is to provide LncRNA-TUG1 to regulate and control periodontal ligament stem cell in preparation
Stemness maintain ability drug in application.
To achieve the above object, the present invention adopts the following technical scheme:
The first aspect of the present invention provides LncRNA-TUG1 as biomarker and regulates and controls periodontal ligament stem cell in preparation
Stemness maintain ability drug in application.
The second aspect of the present invention provides LncRNA-TUG1 promotor in the dry of preparation positivity regulation periodontal ligament stem cell
Property maintain ability drug in application.
In above-mentioned application, the LncRNA-TUG1 promotor refers to any activity that LncRNA-TUG1 can be improved, increases
Add the substance of LncRNA-TUG1 expression quantity, such as increases the over-express vector of the LncRNA-TUG1 of LncRNA-TUG1 expression quantity.
In above-mentioned application, it includes: to promote parodontium dry thin that the stemness of the positivity regulation periodontal ligament stem cell, which maintains ability,
The proliferative capacity of born of the same parents, the Multidirectional Differentiation ability for promoting periodontal ligament stem cell, the transfer ability for promoting periodontal ligament stem cell and promotion
The ability of cell stemness correlation factor expression.
The third aspect of the present invention provides LncRNA-TUG1 inhibitor in the dry of preparation negativity regulation periodontal ligament stem cell
Property maintain ability drug in application.
In above-mentioned application, the LncRNA-TUG1 inhibitor includes antagonist, lower adjustment, retarding agent, blocking agent etc..
Any activity that can reduce LncRNA-TUG1, the substance for reducing LncRNA-TUG1 expression quantity are used equally for the present invention.
Preferably, the LncRNA-TUG1 inhibitor is the slow virus carrier for inhibiting LncRNA-TUG1 expression.
In above-mentioned application, it includes: to inhibit parodontium dry thin that the stemness of the negativity regulation periodontal ligament stem cell, which maintains ability,
The proliferative capacity of born of the same parents, the Multidirectional Differentiation ability for inhibiting periodontal ligament stem cell, the transfer ability for inhibiting periodontal ligament stem cell and inhibition
The ability of cell stemness correlation factor expression.
The fourth aspect of the present invention, the stemness for providing a kind of regulation periodontal ligament stem cell maintain the pharmaceutical composition of ability,
Described pharmaceutical composition contains a effective amount of above-mentioned LncRNA-TUG1 promotor or LncRNA-TUG1 inhibitor.
Further, also include in described pharmaceutical composition: pharmaceutically acceptable carrier.
" pharmaceutically acceptable carrier " is conventional drug administration carrier, including various excipient or diluent etc..
Above-mentioned technical proposal has the following beneficial effects:
Make present invention firstly discovers that LncRNA-TUG1 has played important regulation in periodontal ligament stem cell stemness maintenance process
With when LncRNA-TUG1 is lowered, the proliferation of PDLSCs, self-renewing, differentiation, transfer ability are suppressed, thereby confirm that
LncRNA-TUG1 can be used as the potential target spot of multipotential stem cell stemness maintenance, and promotion is developed new about LncRNA-TUG1 phase
Drug or the factor are closed, and is finally applied to regenerative medicine field, reaches clinically really precisely medical treatment.
Detailed description of the invention
The accompanying drawings constituting a part of this application is used to provide further understanding of the present application, and the application's shows
Meaning property embodiment and its explanation are not constituted an undue limitation on the present application for explaining the application.
Fig. 1: the biological characteristic research result of periodontal ligament stem cell；A is the PDLSCs (P0) of originally culture；B is third
Be commissioned to train feeding PDLSCs (P3)；C is the qualification result of stem cell surface marker；D and E is respectively PDLSCs skeletonization to, fat
To the ability of induction differentiation.A, Scale bar:200 μm in B, D, E.
Fig. 2: slow virus carrier transfect PDLSCs to reduce TUG1 expression .A. immunofluorescence dyeing (scale bar:
200um)；B.qRT-PCR.
Fig. 3: TUG1 to periodontal ligament stem cell proliferative capacity, the influence of Cellular cycle and apoptosis ability；In figure, A.EdU is aobvious
Show the proliferative capacity of sh-NC and sh-TUG1-2# group；B.CCK-8 Faxian shows the proliferative capacity of sh-NC and sh-TUG1-2# group；
C.MTT Faxian shows the proliferative capacity of sh-NC and sh-TUG1-2# group；D. colony formation shows sh-NC and sh-TUG1-2#
The cell Proliferation and self-renewal capacity of group；E, influence of the F.TUG1 to periodontal ligament stem cell Cellular cycle and apoptosis ability.(with
P < 0.05 is statistically significant；* p < 0.05, p < 0.01 * *), Scale bar:200 μm in A, D.
Fig. 4: the TUG1 influence to Periodontal ligament stem cell Multidirectional Differentiation ability；In figure, A, B.ALP dye (7d) and ALP
Activity；C, D. Alizarin red staining (21d) and calcium ion concentration；E. expression feelings of the skeletonization to correlation factor (ALP, Runx2, OCN)
Condition；F, G, H. oil red O stain and the expression at fatty correlation factor.A, Scale bar:200 μm in C, F.
Sh-TUG1-2# group is on a declining curve compared with empty carrier group as the result is shown.(statistically significant with p < 0.05 *).
Fig. 5: the TUG1 influence to Periodontal ligament stem cell transfer ability；In figure, A is Transwell experiment；B is scratch
Experiment；Sh-TUG1-2# group is in reducing tendency, Scale bar:200 μ compared with the transfer ability of empty carrier group (sh-NC) as the result is shown
m.(statistically significant with p < 0.05 *).
Fig. 6: the TUG1 influence to Periodontal ligament stem cell stemness correlation factor；In figure, A. stemness correlation factor mRNA water
Flat variation；B. the variation of stemness correlation factor protein level.
Specific embodiment
It is noted that described further below be all exemplary, it is intended to provide further instruction to the present invention.Unless another
It indicates, all technical and scientific terms used herein has usual with general technical staff of the technical field of the invention
The identical meanings of understanding.
It should be noted that term used herein above is merely to describe specific embodiment, and be not intended to restricted root
According to exemplary embodiments of the present invention.As used herein, unless the context clearly indicates otherwise, otherwise singular
Also it is intended to include plural form, additionally, it should be understood that, when in the present specification using term "comprising" and/or " packet
Include " when, indicate existing characteristics, step, operation and/or their combination.
As background technique is introduced, do not maintained at present about the stemness of LncRNA regulation Periodontal ligament stem cell also
The report of ability.Based on this, the present invention regulates and controls the experiment in vitro that PDLSCs stemness maintains ability by LncRNA-TUG1, and right
Its related mechanism carries out Molecular level study, and the stemness for proposing LncRNA-TUG1 in preparation regulation periodontal ligament stem cell maintains
New application in the drug of ability.
In order to enable those skilled in the art can clearly understand technical solution of the present invention, below with reference to tool
The embodiment of the body technical solution that the present invention will be described in detail.
Embodiment 1: the biological characteristic research of periodontal ligament stem cell
1. the separation and culture of Periodontal ligament stem cell
It is sterile under anesthesia to pull out people's impacted third molar, surrounding periodontium is gently removed, the periodontal group in middle section is taken
It knits, is cleaned, shredded repeatedly with PBS, be placed in the digestive juice of enzyme containing Type I collagen (3g/L) and II enzyme of Dispase (4g/L), at 37 DEG C
Digestion 40 minutes crosses 70um cell sieve and collects cell, 1000 revs/min, is centrifuged 5 minutes, removes the liquid on upper layer, with fresh
Culture solution suspends into single cell suspension again.By cell inoculation in 25cm2In Tissue Culture Flask, (contain 15% in α-MEM culture medium
Fetal calf serum, 2mmol/L glutamine, 100U/ml penicillin and 100 μ g/ml streptomysins) in 37 DEG C, 5%CO2Culture, every
It changes within 2-3 days liquid 1 time, observes cell growth condition under inverted phase contrast microscope.When cell grows to 80% converging state, use
0.25% trypsase presses 1:2 or 1:3 had digestive transfer culture.
The result is shown in Figure 1 A and Figure 1B.
2. the expression of self-renewal capacity detection and periodontal ligament stem cell marker
Using flow cytometry, periodontal ligament stem cell STRO-1, CD146, CD45, the mescenchymal stem cells mark such as CD31 are observed
The expression of will object.
The result is shown in Figure 1 C.
3. Multidirectional Differentiation ability detects
Periodontal ligament stem cell is cultivated 3 weeks into induced medium to induced medium and fat in skeletonization respectively, then
Its multi-lineage potential is detected by Alizarin red staining, oil red O stain and RT-PCR technology respectively.
The result is shown in Figure 1 D and Fig. 1 E.
The PDLSCs being separately cultured it can be seen from the above results can be divided into osteoblast, rouge by identification and induction
Fat cell etc. has the multi-lineage potential of stem cell.
Embodiment 2:LncRNA-TUG1 maintains the regulation of ability to influence periodontal ligament stem cell stemness
1. the building of slow virus carrier:
According to people LncRNA-TUG1 sequence (ID:55000) design primer, primer is by the limited public affairs of Shanghai neck section biotechnology
Department synthesizes and purifies.The pGenesil-1 plasmid of linearisation is connected to after annealing, the expression of building LncRNA-TUG1 (silencing) carries
Body slow virus inhibits the expression of LncRNA-TUG1.
It is specific as follows:
Vector:pLenO-GFP
Lenti-human-NC sequence: TTCTCCGAACGTGTCACGT (SEQ ID NO:1)；(Negative
Control)。
Lenti-human-sh1 TUG1
GPH-hTUG1-SH1 Forward Sequence
5’-GATCCCTGTTGACCTTGCTGTGAGAACTTCCTGTCAGATTCTCACAGCAAGGTCAACAGTTTTTG-
3'(SEQ ID NO:2)；
GPH-hTUG1-SH1 Reverse Sequence
5’-AATTCAAAAACTGTTGACCTTGCTGTGAGAATCTGACAGGAAGTTCTCACAGCAAGGTCAACAGG-
3’(SEQ ID NO:3)。
Lenti-human-sh2 TUG1
GPH-hTUG1-SH2 Forward Sequence
5’GATCCGCTTGGCTTCTATTCTGAATCCTTTCTTCCTGTCAGAAAAGGATTCAGAATAGAAGCCAAG
CTTTTTG3'(SEQ ID NO:4)；
GPH-hTUG1-SH2 Reverse Sequence
5’-AATTCAAAAAGCTTGGCTTCTATTCTGAATCCTTTTCTGACAGGAAGAAAGGATTCAGAATAGAA
GCCAAGCG-3’(SEQ ID NO:5)。
Lenti-human-sh3 TUG1
GPH-hTUG1-SH3 Forward Sequence
5’-GATCCGCTACAACTATCTTCCTTTACCTTCCTGTCAGAGTAAAGGAAGATAGTTGTAGCTTTTTG-
3'(SEQ ID NO:6)；
GPH-hTUG1-SH3 Reverse Sequence
5’-AATTCAAAAAGCTACAACTATCTTCCTTTACTCTGACAGGAAGGTAAAGGAAGATAGTTGTAGCG-
3’(SEQ ID NO:7)。
Lenti-human-sh4 TUG1
GPH-hTUG1-SH4 Forward Sequence
5’-GATCCGCAAGAGATAACTATGAAAGCCTTCCTGTCAGAGCTTTCATAGTTATCTCTTGCTTTTTG-
3'(SEQ ID NO:8)；
GPH-hTUG1-SH4 Reverse Sequence
5’-AATTCAAAAAGCAAGAGATAACTATGAAAGCTCTGACAGGAAGGCTTTCATAGTTATCTCTTGCG-
3’(SEQ ID NO:9)。
The different slow virus carriers of building are investigated to the silencing efficiency of LncRNA-TUG1, as a result see Fig. 2.It can be seen by Fig. 2
Out, the silencing efficiency of sh-TUG1-2# is most obvious.Therefore, subsequent experimental study is used for sh-TUG1-2#.
2. test grouping:
Test is divided into three groups, is respectively as follows: Control group, sh-NC group, sh-TUG1-2# group.
Cell is cleaned with serum free medium, sh-TUG1-2# and sh-NC empty carrier adds according to transfection procedure specification
Enter into cell.It uses normal culture medium after 8-10h instead, in fluorescence microscopy microscopic observation after being incubated for for 24 hours, green fluorescence occurs and say
Bright transfect successfully completes the associated verification that subsequent stemness maintains ability.
3. cell proliferation experiment:
EdU, MTT, CCK-8 method and colony formation detect cell proliferation rate；Cell cycle and apoptosis experiment detect it
Influence to cell characteristics, is as a result shown in Fig. 3.
As seen from Figure 3, the proliferative capacity of silencing LncRNA-TUG1, cell weaken, apoptosis capacity enhancing.
4. Multidirectional Differentiation ability detects:
(1) skeletonization is measured to differentiation capability:
ALP dyeing and Alizarin red staining, and ALP activity, calcium ion concentration measurement are carried out, it is detected by real-time quantitative PCR
The expression of skeletonization key factor Runx2, ALP and OCN gene changes.
(2) it is measured at rouge to differentiation capability:
Carry out oil red dyeing and the measurement of PPAR γ and the LPL factor.
The result of Multidirectional Differentiation ability detection is as shown in Figure 4.As seen from Figure 4, silencing LncRNA-TUG1, cell
Skeletonization to at fat to reduced capability.
5. transfer ability detects:
Transfer ability is detected using Transwell and scratch experiment, as a result as shown in Figure 5.There is Fig. 5 that can see
Out, the transfer ability of silencing LncRNA-TUG1, cell weaken.
6. the measurement of stemness correlation factor:
The mRNA and protein level of stemness correlation factor are measured, as a result as shown in Figure 6.As seen from Figure 6, it sinks
Silent LncRNA-TUG1, the expression of cell stemness correlation factor weaken.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention,
It should be equivalent substitute mode, be included within the scope of the present invention.
SEQUENCE LISTING
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Claims (7)
1.LncRNA-TUG1 promotor answering in the drug that the stemness of preparation positivity regulation periodontal ligament stem cell maintains ability
With.
2. application as described in claim 1, which is characterized in that the LncRNA-TUG1 promotor is to increase LncRNA-TUG1
The over-express vector of the LncRNA-TUG1 of expression quantity.
3. application as described in claim 1, which is characterized in that the stemness of the positivity regulation periodontal ligament stem cell maintains ability
Include: the proliferative capacity for promoting periodontal ligament stem cell, the Multidirectional Differentiation ability for promoting periodontal ligament stem cell, promote parodontium dry thin
The transfer ability of born of the same parents and the ability for promoting the expression of cell stemness correlation factor.
4.LncRNA-TUG1 inhibitor answering in the drug that the stemness of preparation negativity regulation periodontal ligament stem cell maintains ability
With.
5. application as claimed in claim 4, which is characterized in that the LncRNA-TUG1 inhibitor includes: LncRNA-TUG1
Antagonist, it is lower adjust, retarding agent or blocking agent.
6. application as described in claim 4 or 5, which is characterized in that the LncRNA-TUG1 inhibitor is to inhibit LncRNA-
The slow virus carrier of TUG1 expression.
7. application as claimed in claim 4, which is characterized in that the stemness of the negativity regulation periodontal ligament stem cell maintains ability
Include: the proliferative capacity for inhibiting periodontal ligament stem cell, the Multidirectional Differentiation ability for inhibiting periodontal ligament stem cell, inhibit parodontium dry thin
The transfer ability of born of the same parents and the ability for inhibiting the expression of cell stemness correlation factor.
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| WO2016129633A1 (en) * | 2015-02-10 | 2016-08-18 | 公立大学法人名古屋市立大学 | Antitumor agent |
| CN106520771A (en) * | 2016-12-20 | 2017-03-22 | 江苏省人民医院 | Long non-coding RNA and application of long non-coding RNA in diagnosis and treatment of preeclampsia |
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| WO2016129633A1 (en) * | 2015-02-10 | 2016-08-18 | 公立大学法人名古屋市立大学 | Antitumor agent |
| CN106520771A (en) * | 2016-12-20 | 2017-03-22 | 江苏省人民医院 | Long non-coding RNA and application of long non-coding RNA in diagnosis and treatment of preeclampsia |
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| Overexpression of TUG1 attenuated cold‐induced cell injury via blocking mitochondrial apoptosis‐dependent pathway and ER stress pathway;Song Su et al.;《The FEBS Journal》;20161231;第283卷;第1261-1274页 |
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