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

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.

Depth Dependent Variations in Human Achilles Tendon as a Result of Active Smoking: An Elastographic Study

Current study was set to determine the impact of active smoking on Achilles Tendon (AT) as soft tissue using an elastographic technique. This study comprises of 54 male individuals having sedentary lifestyle. Volunteers were categorized into two groups of smokers (n = 20) and non-smokers (n = 34). Body composition analysis was performed to evaluate the physiological changes in human body mass indexes. Ultrasound Strain Elastog-raphy (USE) technique was used to find the stiffness along with anatomical images to envisage the anomalous status of Achilles tendon. Statistical analysis of data obtained through body composition, tendon anatomy and Strain Elastography (SE) was used to scrutinize the physiological, anatomical and elasticity variations within the tendon. A reduction in Fat Free Mass Index (FFMI) was observed among smokers with a significant difference (P = 0.042). Further, an increased significant difference (P = 0.029) was found in AT Strain Ratios (SR) of smokers as compared to non-smokers. Lightening in tendon mass and dilution in tendon stiffness indicates that smoking mechanism may generate excessive apoptosis and decrease the density of tenocytes. Nicotine is the key element that inhibits the functional capacity of Tendon Stem Cells and is highly responsible for tendinopathy, eventually leading to tendon rupture and injury.

Co-cultured Bone-marrow Derived and Tendon Stem Cells: Novel Seed Cells for Bone Regeneration

Tendon-bone healing after injury is an unsolved problem. Several types of stem cells are used as seed cells. However, the optimal co-culture ratio of different types of cells suitable for tissue engineering as well as the stimulator for facilitating the differentiation of stem cells in tendon-bone healing is unclear. In this study, the proliferation of both bone marrow-derived stem cells (BMSCs) and tendon stem cells (TSCs) was increased at a 1:1 co-cultured ratio, and proliferation was suppressed by Tenascin C (TNC). TNC treatment can promote osteogenesis or chondrogenesis of both BMSCs and TSCs under a 1:1 co-cultured ratio. In addition, the expression level of Rho-associated kinase (ROCK) increased in the process of TNC-induced osteogenesis and decreased in the process of TNC-induced chondrogenesis. Furthermore, the level of insulin-like growth factor 1 receptor (IGF-1R) and mitogen-activated protein kinase (MEK) was upregulated during the osteogenesis and chondrogenesis of both BMSCs and TSCs after TNC treatment. Although our study was conducted in rats with no direct evaluation of the resulting cells for tendon-bone healing and regeneration, we show that the proliferation of BMSCs and TSCs was enhanced under a 1:1 co-cultured ratio. TNC has a significant impact on the proliferation and differentiation of co-cultured BMSCs and TSCs. IGF-IR, ROCK, and MEK may become involved in the process after TNC treatment.