scholarly journals Mechanical Tension Promotes the Osteogenic Differentiation of Rat Tendon-derived Stem Cells Through the Wnt5a/Wnt5b/JNK Signaling Pathway

2015 ◽  
Vol 36 (2) ◽  
pp. 517-530 ◽  
Author(s):  
Xiangzhou Liu ◽  
Wan Chen ◽  
You Zhou ◽  
Kanglai Tang ◽  
Jiqiang Zhang
Keyword(s):  
Stem Cells ◽  
Protein Expression ◽  
Osteogenic Differentiation ◽  
Heterotopic Ossification ◽  
Signaling Pathway ◽  
Sports Injury ◽  
Tendon Tissue ◽  
Mechanical Tension ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway

Background/Aims: Tendinopathy is a common sports injury that is manifested by the heterotopic ossification of tendon tissue. Tendon stem cells (TSCs) are prone to osteogenic differentiation under excessive tension. The underlying mechanisms remain poorly understood. Methods: Uniaxial mechanical tension (UMT) served to stretch rat tendon-derived stem cells (rTDSCs) at 8% elongation (frequency: 1 Hz; 48, 60, or 72 hours). Results: The osteogenic differentiation of rTDSCs appeared after UMT along with increased mRNA expression of the osteogenic genes Runx2, Dlx5, Alpl, and Col1a1 and increased Runx2 protein expression. Wnt5a, Wnt5b and P-JNK protein levels were also upregulated after UMT stimulation. The inhibition of JNK expression by SP600125 and JNK1-shRNA decreased UMT-induced Runx2 protein expression, and the activation of JNK expression by anisomycin and JNK1-cDNA increased UMT-induced Runx2 protein expression. When shRNA knocked down Wnt5a and Wnt5b expression in rTDSCs, the induction of Runx2 and P-JNK expression by UMT was reduced. The inhibition of Runx2 expression could be rescued by the activation of JNK expression by anisomycin. Conclusion: UMT induced the osteogenic differentiation of rTDSCs via the Wnt5a/Wnt5b/JNK signaling pathway. Accordingly, this pathway may influence the heterotopic ossification of tendon tissue subjected to excessive tension.

scholarly journals IL-6 Promotes Osteogenic Differentiation of Rat Tendon Stem Cells through the STAT3/Wnt5a Signalling Pathway

2021 ◽  
Author(s):  
Xiangzhou Liu ◽  
Ying Jin ◽  
Xiuqi Liu ◽  
Jiachen Peng
Keyword(s):  
Stem Cells ◽  
Protein Expression ◽  
Osteogenic Differentiation ◽  
Sports Injury ◽  
Signalling Pathway ◽  
Ectopic Ossification ◽  
Alkaline Phosphatase Staining ◽  
Culture Model ◽  
Tendon Stem Cells ◽  
Mrna And Protein Expression

Abstract Background: Tendinopathy is currently the common clinical condition related to sports injury. The main pathological change in tendinopathy is ectopic ossification in tendon tissue, but the mechanisms have remained elusive. Studies have found that interleukin-6 (IL-6) is a major inflammatory mediator in chronic tendinopathy, and osteogenic differentiation of tendon stem cells (TSCs) is believed to be closely related to ectopic ossification of tendons. Methods: Rat tendon-derived stem cell (rTDSC) culture model, Lentivirus transfection, Alkaline phosphatase staining, Real-time PCR and Western blotting were performed in this study.Results: We showed that after IL-6 induction, the mRNA expression of Runx2, Alpl, Dlx5, and Wnt5a and the protein expression of phosphorylated STAT3, Runx2, and Wnt5a were increased in rTDSCs. Wnt5a shRNA and cDNA induced silencing and overexpression of Wnt5a inhibited and promoted osteogenic differentiation of rTDSCs, respectively. The addition of a STAT3 inhibitor inhibited osteogenic differentiation and Wnt5a mRNA and protein expression in rTDSCs, and this inhibition was reversed by cDNA induced Wnt5a overexpression. Conclusion: We concluded that IL-6 promotes osteogenic differentiation of rTDSCs through the STAT3/Wnt5a signalling pathway.

scholarly journals Gremlin 2 Promotes Differentiation of Embryonic Stem Cells to Atrial Fate by Activation of the JNK Signaling Pathway

Stem Cells ◽  
2014 ◽  
Vol 32 (7) ◽  
pp. 1774-1788 ◽  
Author(s):  
Vineeta Tanwar ◽  
Jeffery B. Bylund ◽  
Jianyong Hu ◽  
Jingbo Yan ◽  
Joel M. Walthall ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Signaling Pathway ◽  
Embryonic Stem ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway

scholarly journals N-CoR modulates osteogenic differentiation of rat mesenchymal stem cells through the PI3K/Akt-cell signaling pathway

2016 ◽  
Vol 68 (3) ◽  
pp. 551-559
Author(s):  
Yi Qin ◽  
Guoping Cao ◽  
Jichao Ye ◽  
Peng Wang ◽  
Liangbin Gao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Protein Expression ◽  
Osteogenic Differentiation ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Pathway ◽  
Akt Signaling Pathway ◽  
Alp Activity

The nuclear receptor corepressor (N-CoR) is involved in the regulation of diverse transcription factors. We previously found that N-CoR could regulate adipogenic differentiation of rat mesenchymal stem cells (MSCs),but whether it modulated osteogenic differentiation of this type of cells was uncertain. Therefore, in the present study, we investigated the effect and mechanism of N-CoRon osteogenic differentiation of rat MSCs. The results showed that MSCs cultured in osteogenic medium successfully differentiated into osteogenic cells. Overexpression of N-CoR decreased cell proliferation, alkaline phosphatase (ALP)activity, calcium accumulation, mRNA expression of genes including bone sialoprotein (BSP), osteocalcin (OCN), osteopontin (OPN), Osterix and Runx2, and protein expression of phosphor-Akt(pAkt). Conversely, knocking down cellular N-CoR by small interfering RNA (siRNA) promoted pAkt activity and cell differentiation. Overexpression or knockdown of N-CoRhad no significant influences on the protein expression of pyruvate dehydrogenase kinase isozyme 1 (PDK1), phosphatidylinositol 3-kinase (PI3K) and total Akt, indicating that N-CoR regulated the changes in the PI3K/Akt signaling pathway by targeting pAkt. To further prove the function of the PI3K/Akt signaling in N-CoR-regulated osteogenic differentiation, we used the PI3K inhibitor (LY294002) to block the activation of the PI3K/Akt pathway and found that overexpression of N-CoR showed no effects on ALP activity, calcium level and mRNA expression of BSP, osteocalcin OCN, OPN, Osterix and Runx2 in rat MSCs following the inhibition of the PI3K/Akt pathway. These findings suggest that N-CoR regulates osteogenic differentiation of rat MSCs through suppression of the PI3K/Akt signaling pathway.

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