BMP7 induces the differentiation of bone marrow-derived mesenchymal cells into chondrocytes

Abstract

Injured articular cartilage has a poor capacity for spontaneous healing. So far, a satisfactory solution to repair the injured cartilage has not been found, but transgenic therapy might be a promising treatment. This study aims to evaluate the potential of transfecting bone morphogenetic protein-7 (BMP-7), a secretory protein, into bone marrow-derived mesenchymal stem cells (BMSCs), in inducing the differentiation of bone marrow stromal cells into chondrocytes in vitro. The phenotypes of the cells were observed by alcian blue staining and H&E staining with an inverted microscope. The glycosaminoglycan (GAG) content of BMSCs transfected with pcDNA3.1-BMP7 or induced by inducing medium was examined after 7, 14, or 21 days of incubation. A standard curve as reference for BMSCs' GAG content was plotted using galacturonic acid. The content of type II collagen in culture medium was detected by ELISA. Our results demonstrated that BMP7-transfected BMSCs or BMSCs incubated with inducing medium possess the ability to differentiate into chondrocytes. BMP7-induced BMSCs secrete type II collagen and GAG. There was no significant difference between BMP7-induced BMSCs in their secreted protein content when compared with the positive control group (TGF-β1 and dexamethasone) (P > 0.05), but there was significant difference in the secreted protein profile when compared with the negative control group (P < 0.05).

Gene Expression Profile during Chondrogenesis in Human Bone Marrow derived Mesenchymal Stem Cells using a cDNA Microarray

“…Recent studies have confirmed that BMP-7 is a strong chemotactic component in cartilage cells produced by mesenchymal stem cells, and it can promote cartilage cells to secrete specific extracellular matrix (proteoglycans and collagen type II). And BMP-7 can induce the differentiation of BM-MSCs into cartilage cells, and that it offers a greater efficiency in repairing cartilage and subchondral bone defects (16).…”

Genetic Engineering of Mesenchymal Stem Cells for Regenerative Medicine

“…TGF-β1 [78,79,80] TGF-β3 [81,82] CDMP1 [83] IGF-1/BMP-2 [85] IGF-1/FGF-2 [90] BMP-7 [88] Wnt11 [91] So So ZN…”

“…The appropriate chondrogenenic process was appreciated in these so-transformed cells [85], despite the fact that the overexpression [86] and the treatment of BMP-2 alone is reported to facilitate osteogenesis in MSCs [87]. There is an example of the application of another BMP family member, BMP7, in which the BMP7 gene transfection of BM-MSCs resulted in favorable chondrocyte formation [88]. Interestingly, the IGF-1 overexpression was able to stimulate the expression of the Sox9 gene; however, the expression of osteogenic marker genes was also elevated, suggesting that IGF-1 gene transfections into BM-MSCs with chondrogenic purposes should be considered cautiously [89].…”

Matrigel scaffold combined with Ad-hBMP7-transfected chondrocytes improves the repair of rabbit cartilage defect

“…There is evidence that BMP7 is able to induce the differentiation of bone marrow-derived mesenchymal cells into chondrocytes (19) and might serve as an anabolic activator for chondrocytes in tissue culture (20). In addition, clinical studies have revealed that BMP7 is able to prevent the degeneration of cartilage during inflammatory arthritis (21,22).…”