The role of BMP6 in the proliferation and differentiation of chicken cartilage cells

Abstract

Previous studies have indicated that bone morphogenetic protein (BMP) 6 may play an important role in skeletal system development and progression. However, the mechanism underlying the effects of BMP6 in cartilage cell proliferation and differentiation remains unknown. In this study, cartilage cells were isolated from shanks of chicken embryos and treated with different concentrations of Growth Hormone. Cell proliferation potential was assessed using real-time polymerase chain reaction (RT-PCR), western blotting and CCK-8 assays in vitro. The results showed that at 48 h, the Collagen II and BMP6 expression levels in 50 ng/μl GH-treated cartilage cells were significantly higher than in groups treated with 100 ng/μl or 200 ng/μl GH. We further observed that knockdown of BMP6 in cartilage cells led to significantly decreased expression mRNAs and proteins of Collagen II and Collagen X. Moreover, the suppression of BMP6 expression by a specific siRNA led to significantly decreased expression mRNA levels of IGF1R, JAK2, PKC, PTH, IHH and PTHrP and decreased protein levels of PKC, IHH and PTHrP. Taken together, our data suggest that BMP6 may play a critical role in chicken cartilage cell proliferation and differentiation through the regulation of IGF1, JAK2, PKC, PTH, and IHH-PTHrP signaling pathways.

Synergistic interaction of hTGF-β3 with hBMP-6 promotes articular cartilage formation in chitosan scaffolds with hADSCs: implications for regenerative medicine

“…Our results unequivocally demonstrated that hTGFβ 3 alone causes endochondral cartilage formation tending towards ossification rather than true articular cartilage development, unless it is counteracted or synergizes with another TGF-β supergene family member(s) that modulate better the process of articular cartilage formation, here hBMP-6. Although the current literature does not explicitly state this, as it generalizes more on the term chondrogenesis [47,48], we can now with a better degree of certainty claim that the synergetic effect of hBMP-6 with hTGF-β 3 causes "articular" chondrogenesis.…”

“…At the same time, BMP-6 is also a known factor involved in the induction of bone formation [46], indicating a multifunctionality in the regulation of bone and cartilage cell development similar to most BMPs and other growth factors of the TGF-β superfamily. Though diverse groups have shown that BMP-6 can stimulate chondrocyte and cartilage formation [47,48], to date results remain unspecific as to whether hyaline articular or endochondral ossification type cartilage is formed, making interpretations or validations problematic.…”

Growth factors in the initial stage of bone formation, analysis of their expression in chondrocytes from epiphyseal cartilage of rat costochondral junction

“…BMP-6 is highly expressed during proliferation and differentiation of chondrocytes from shanks of 15-day-old chicken embryos. When its expression decreases, the proliferation and differentiation of chondrocytes are blocked [53]. BMP-5 and BMP-6 induce the formation of cartilage and bone in the rat subcutaneous transplant model, but the former requires higher doses for similar osteoinduction [31].…”

Uncovering pathways regulating chondrogenic differentiation of CHH fibroblasts

“…The two most abundant BMPs in the growth plate are BMP-2 and BMP-6 [ 65 , 66 ]. These BMPs drive chondrocytes from a quiescent to a proliferative state, and finally towards their terminal differentiation [ 67 ].…”