Hypertrophic differentiation during chondrogenic differentiation of progenitor cells is stimulated by BMP-2 but suppressed by BMP-7

Abstract

BMP-2 and BMP-7 display opposing actions on the chondrogenic outcome of differentiating progenitor cells: BMP-2 acts a specific inducer of chondrocyte hypertrophy, while BMP-7 appears to increase or maintain chondrogenic potential and prevent chondrocyte hypertrophy. Our results pave the way for an application-dependent differential use of BMP-2 or BMP-7.

Direct bone morphogenetic protein 2 and Indian hedgehog gene transfer for articular cartilage repair using bone marrow coagulates

“…To further explore differences in IHH and BMP2 induced chondrogenesis, we have performed the immunolocalization of type X collagen as a marker of chondrocyte hypertrophy. We have only observed a marked type X collagen deposition in the BMP2 treated joints with severe intralesional bone formation, confirming previous in vitro experiments which described the increased expression of hypertrophy markers after BMP2 treatment of multipotent cells 6,12,28 . We recommend caution towards the application of BMP-2 or BMP2 gene transfer for cartilage repair due to the risk of osteophyte formation, particularly in conjunction with marrow stimulating techniques, which has been recommended previously 29 .…”

“…BMP-2 is affecting gene expression via members of the SMAD protein family or mitogen-activated protein (MAP) kinase pathways after binding to BMP type I and type II receptors at the cell membrane 10,11 . However, along with other factors, it was observed to induce chondrocyte hypertrophy in osteoarthritis (OA), growth plate cartilage and adult mesenchymal stem cells (MSCs) in vitro 2,6,12 . While the induction of intralesional hypertrophy and bone formation in cartilage defects by BMP-2 was discussed previously, there is only limited data on this topic to date 2 .…”

Signaling Pathways in Cartilage Repair

“…Moreover, blocking BMP activity resulted in a reduced synthesis of proteoglycan [52] and increased cartilage damage [56]. Conversely, BMP-2 induces hypertrophic differentiation of chondrocytes and may promote cartilage degradation by elevating MMP-13 expression, as observed in OA cartilage [57,58]. The requirement of BMPs for chondrocyte terminal differentiation is highlighted by the evidence that loss of Smad 1 and 5 or inhibition of the Smad 1/5/8 signaling cascade blocks the differentiation of chondrocytes and leads to severe cartilage defects [59,60].…”

A post-translational modification cascade employing HDAC9-PIASy-RNF4 axis regulates chondrocyte hypertrophy by modulating Nkx3.2 protein stability

“…Interestingly, Nkx3.2 expression is maintained in early stage immature and proliferative chondrocytes, whereas its expression is suppressed upon the onset of chondrocyte hypertrophy during terminal stages of chondrogenesis [7][8][9]. Consistent with this expression pattern, forced expression of Nkx3.2 can inhibit chondrocyte maturation [10,11].…”