Higher BMP receptor expression and BMP-2-induced osteogenic differentiation in tendon-derived stem cells compared with bone-marrow-derived mesenchymal stem cells

Abstract

Surgical reattachment of tendon to bone often fails due to regeneration failure of the specialised tendon-bone junction (TBJ). The use of mesenchymal stem cells for TBJ regeneration has been reported with promising results. Tendon-derived stem cells (TDSCs) with high proliferative and multi-lineage differentiation potential have been isolated. As stem cells residing in tendons, TDSCs can be considered a new cell source for TBJ repair. Bone morphogenic protein 2 (BMP-2) is a potent osteogenic factor with roles in normal bone healing and pathological ectopic bone formation in soft tissues. The use of BMP-2 to promote TBJ repair has been well reported. This study aimed to compare TDSCs to the gold standard bone-marrow-derived mesenchymal stem cells (BMSCs) with respect to osteogenic response to BMP-2 in vitro. The clonogenicity and multi-differentiation potential of TDSCs and BMSCs were identified by colony-forming-unit assay, osteogenic, adipogenic and chondrogenic differentiation assays. Their osteogenic response to BMP-2 in vitro was examined by alkaline phosphatase (ALP) cytochemical staining, ALP activity assay and Alizarin red S staining of calcium nodule formation. Messenger RNA (mRNA) and BMP receptor (types IA, IB and II) protein expression were examined by quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. Our results showed that both TDSCs and BMSCs exhibited stem cell properties, including clonogenicity and multi-differentiation potential. TDSCs expressed higher mRNA and protein levels of BMP receptors IA, IB and II. They also exhibited higher osteogenic differentiation with and without BMP-2 stimulation compared with BMSCs. TDSCs with/without BMP-2 might be an attractive source for TBJ repair compared with BMSCs.