BMP-9 Improves the Osteogenic Differentiation Ability over BMP-2 through p53 Signaling In Vitro in Human Periosteum-Derived Cells

Abstract

Bone morphogenetic proteins (BMPs) have tremendous therapeutic potential regarding the treatment of bone and musculoskeletal disorders due to their osteo-inductive ability. More than twenty BMPs have been identified in the human body with various functions, such as embryonic development, skeleton genesis, hematopoiesis, and neurogenesis. BMPs can induce the differentiation of MSCs into the osteoblast lineage and promote the proliferation of osteoblasts and chondrocytes. BMP signaling is also involved in tissue remodeling and regeneration processes to maintain homeostasis in adults. In particular, growth factors, such as BMP-2 and BMP-7, have already been approved and are being used as treatments, but it is unclear as to whether they are the most potent BMPs that induce bone formation. According to recent studies, BMP-9 is known to be the most potent inducer of the osteogenic differentiation of mesenchymal stem cells, both in vitro and in vivo. However, its exact role in the skeletal system is still unclear. In addition, research results suggest that the molecular mechanism of BMP-9-mediated bone formation is also different from the previously known BMP family, suggesting that research on signaling pathways related to BMP-9-mediated bone formation is actively being conducted. In this study, we performed a phosphorylation array to investigate the signaling mechanism of BMP-9 compared with BMP-2, another influential bone-forming growth factor, and we compared the downstream signaling system. We present a mechanism for the signal transduction of BMP-9, focusing on the previously known pathway and the p53 factor, which is relatively upregulated compared with BMP-2.

Periosteum Containing Implicit Stem Cells: A Progressive Source of Inspiration for Bone Tissue Regeneration

“…Although several BMPs are expressed spatiotemporally in bone and act as essential motivators in bone developmental and regenerative processes, BMP2 has a unique role in PDPCs, and thereby regulates BMP signaling inducing periosteal bone formation, growth, and fracture repair. Neither absence of other BMPs such as BMP4, BMP7, and BMP9 [62] nor BMP2 loss in mature osteoblasts causes spontaneous fractures [63]. Yet, both BMP2 and BMP4 expressions are increased and activate osteogenesis when PDCs respond to mechanical stretch, along with reduction in BMP6 expression [64].…”

“…BMP2 signaling is also essential for the initiation of fracture healing [62,65]. A transgenic BMP2-deficient mouse model showed that local expression of BMP2 played a critical role in osteogenic and chondrogenic differentiation of PDPCs during repair, which eventually induced robust periosteal bone/cartilage callus formation [62,66].…”