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Research Article
Xiaojing Guo
Department of Prosthodontics, Shanghai Stomatological Hospital, Fudan University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6516-0019
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Cartilage regeneration is a key step in functional reconstruction for temporomandibular joint osteoarthritis (TMJ-OA), but is a difficult issue to address. Strontium ranelate (SrR) is an antiosteoporosis drug that has been proven to affect OA in recent years, but its effect on chondrogenesis and the underlying mechanism are still unclear.
Methods
Bone mesenchymal stem cells(BMSCs) from Sprague–Dawley (SD) rats were induced in chondrogenic differentiation medium with or without SrR, XAV-939 and LiCl. CCK-8 assays were used to examine cell proliferation, and alcian blue staining, toluidine blue staining, immunofluorescence and PCR analysis were performed. Western blot (WB) analyses were used to assess chondrogenic differentiation of the cells. For an in vivo study, 30 male SD rats with cartilage defects on both femoral condyles were used. The defect sites were not filled, filled with silica nanosphere plus gelatine-methacryloyl (GelMA) or filled with SrR-loaded silica nanosphere plus GelMA. After 3 months of healing, paraffin sections were made, and toluidine blue staining, safranin O/fast green staining, and immunohistochemical staining were performed for histological evaluation. The data were analysed by SPSS 26.0 software.
Results
Low concentrations of SrR did not inhibit cell proliferation, and the cells treated with SrR (0.25 mmol/L) showed stronger chondrogenesis than the control. XAV-939, an inhibitor of β-catenin, significantly promoted chondrogenesis, and SrR did not suppress this effect, while LiCl, an agonist of β-catenin, strongly suppressed chondrogenesis, and SrR reversed this inhibitory effect. In vivo study showed a significantly better cartilage regeneration by SrR-loaded GelMA than the other treatments.
Conclusion
SrR could promote BMSCs chondrogenic differentiation by inhibiting the Wnt/β-catenin signalling pathway and accelerate cartilage regeneration in rat femoral condyle defects.
Keywords
Strontium ranelate, BMSCs, chondrogenesis, cartilage regeneration, Wnt/β-catenin pathway
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CURRENT STATUS: Under Review
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Posted 02 May, 2021
Reviewer #2 agreed
On 02 May, 2021
Review #2 received
Received 02 May, 2021
Editor assigned
On 27 Apr, 2021
Reviewers invited
Invitations sent on 27 Apr, 2021
Reviewer #1 agreed
On 27 Apr, 2021
Review #1 received
Received 27 Apr, 2021
Submission checks complete
On 27 Apr, 2021
Editor invited
On 27 Apr, 2021
This version was not preprinted
Version 1
Posted 23 Mar, 2021
No community comments so far
Review #2 received
Received 29 Mar, 2021
Editorial decision: Minor Revision
On 29 Mar, 2021
Reviewer #2 agreed
On 22 Mar, 2021
Review #1 received
Received 21 Mar, 2021
Reviews received
Received 20 Mar, 2021
Reviewer #1 agreed
On 20 Mar, 2021
Reviewers invited
Invitations sent on 19 Mar, 2021
First submitted
On 18 Mar, 2021
Editor assigned
On 17 Mar, 2021
Submission checks complete
On 17 Mar, 2021
Editor invited
On 17 Mar, 2021
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Subject Areas
Stem Cell & Developmental Cell Biology
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This preprint is under consideration at Stem Cell Research & Therapy. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Xiaojing Guo
Department of Prosthodontics, Shanghai Stomatological Hospital, Fudan University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6516-0019
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version (no preprint)
Posted 02 May, 2021
Reviewer #2 agreed
On 02 May, 2021
Review #2 received
Received 02 May, 2021
Editor assigned
On 27 Apr, 2021
Reviewers invited
Invitations sent on 27 Apr, 2021
Reviewer #1 agreed
On 27 Apr, 2021
Review #1 received
Received 27 Apr, 2021
Submission checks complete
On 27 Apr, 2021
Editor invited
On 27 Apr, 2021
This version was not preprinted
Version 1
Posted 23 Mar, 2021
No community comments so far
Review #2 received
Received 29 Mar, 2021
Editorial decision: Minor Revision
On 29 Mar, 2021
Reviewer #2 agreed
On 22 Mar, 2021
Review #1 received
Received 21 Mar, 2021
Reviews received
Received 20 Mar, 2021
Reviewer #1 agreed
On 20 Mar, 2021
Reviewers invited
Invitations sent on 19 Mar, 2021
First submitted
On 18 Mar, 2021
Editor assigned
On 17 Mar, 2021
Submission checks complete
On 17 Mar, 2021
Editor invited
On 17 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Stem Cell & Developmental Cell Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Cartilage regeneration is a key step in functional reconstruction for temporomandibular joint osteoarthritis (TMJ-OA), but is a difficult issue to address. Strontium ranelate (SrR) is an antiosteoporosis drug that has been proven to affect OA in recent years, but its effect on chondrogenesis and the underlying mechanism are still unclear.
Methods
Bone mesenchymal stem cells(BMSCs) from Sprague–Dawley (SD) rats were induced in chondrogenic differentiation medium with or without SrR, XAV-939 and LiCl. CCK-8 assays were used to examine cell proliferation, and alcian blue staining, toluidine blue staining, immunofluorescence and PCR analysis were performed. Western blot (WB) analyses were used to assess chondrogenic differentiation of the cells. For an in vivo study, 30 male SD rats with cartilage defects on both femoral condyles were used. The defect sites were not filled, filled with silica nanosphere plus gelatine-methacryloyl (GelMA) or filled with SrR-loaded silica nanosphere plus GelMA. After 3 months of healing, paraffin sections were made, and toluidine blue staining, safranin O/fast green staining, and immunohistochemical staining were performed for histological evaluation. The data were analysed by SPSS 26.0 software.
Results
Low concentrations of SrR did not inhibit cell proliferation, and the cells treated with SrR (0.25 mmol/L) showed stronger chondrogenesis than the control. XAV-939, an inhibitor of β-catenin, significantly promoted chondrogenesis, and SrR did not suppress this effect, while LiCl, an agonist of β-catenin, strongly suppressed chondrogenesis, and SrR reversed this inhibitory effect. In vivo study showed a significantly better cartilage regeneration by SrR-loaded GelMA than the other treatments.
Conclusion
SrR could promote BMSCs chondrogenic differentiation by inhibiting the Wnt/β-catenin signalling pathway and accelerate cartilage regeneration in rat femoral condyle defects.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
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