Abstract
BackgroundEctopic expression of BMP-2, BMP-4 and BMP-7 was observed in clinical samples of tendinopathy and collagenase-induced (CI) tendon injury rat model. TDSCs isolated from the CI model showed increased non-tenogenic differentiation potential and hence altered fate compared to the TDSCs isolated from the healthy animals (HT) but the mechanism is unclear. We hypothesized that sensitization of the BMP/Smad pathway in TDSCs (CI) might account for this difference. This study aimed to compare the activation state of the BMP/Smad pathway at basal level and upon BMP-2 stimulation in TDSCs (CI) and TDSCs (HT).MethodsCollagenase or saline was injected into the patellar tendon of rats for 2 weeks. TDSCs (CI) and TDSCs (HT) were then isolated from the patellar tendon. The mRNA and protein expression of BMPs and BMP receptors in TDSCs (CI) and TDSCs (HT) were analysed. TDSCs from both sources were treated with rhBMP-2 and the expression of phosphorylated and total Smad1/5/8 was examined.ResultsExcept for the mRNA levels of Bmp7 and Bmpr2, there were significant higher mRNA and protein expression of BMPs and BMP receptors in TDSCs (CI) compared to TDSCs (HT). TDSCs (CI) showed higher basal expression of total Smad1/5/8 but similar basal level of phosphorylated Smad1/5/8 compared to TDSCs (HT). TDSCs (CI) exhibited higher total and phosphorylated Smad1/5/8 upon BMP-2 stimulation.ConclusionsThe sensitization of the BMP/Smad pathway in TDSCs (CI) might account for their higher non-tenogenic differentiation potential and hence altered fate. It also provided further support of BMPs and the BMP/Smad signaling pathway in the pathogenesis of tendinopathy.
Highlights
Ectopic expression of BMP-2, BMP-4 and BMP-7 was observed in clinical samples of tendinopathy and collagenase-induced (CI) tendon injury rat model
Our recent data supported this claim as tendon-derived stem cells (TDSCs) (CI) showed altered fate, with higher chondroosteogenic differentiation potential but lower tendonrelated marker expression compared to TDSCs (HT), which might contribute to pathological chondro-ossification and failed tendon healing in this animal model [18]
We showed that the increased expression of BMPs and BMP receptors as well as elevated BMP/Smad sensitivity in TDSCs (CI) might contribute to the increased non-tenogenic differentiation potential and altered fate of these cells
Summary
Ectopic expression of BMP-2, BMP-4 and BMP-7 was observed in clinical samples of tendinopathy and collagenase-induced (CI) tendon injury rat model. With the presence of chondrocyte phenotype [5] and occasional fatty and Ectopic expression of BMP-2, -4 and -7 were observed in clinical samples of tendinopathy [9,10] and collagenaseinduced (CI) tendon injury rat model which showed failed healing and ectopic chondro-ossification in tendons [11]. These BMPs were reported to promote osteogenic, chondrogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) including tendon-derived stem cells (TDSCs) isolated from healthy tendons in vitro [12,13,14,15,16]. Results from this study would provide novel insight of the pathogenic mechanism of tendinopathy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
