Higher BMP/Smad sensitivity of tendon-derived stem cells (TDSCs) isolated from the collagenase-induced tendon injury model: possible mechanism for their altered fate in vitro

BACKGROUND: 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. 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). METHODS: Collagenase 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. RESULTS: Except 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. CONCLUSIONS: The 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.