Magnesium ascorbyl phosphate promotes bone formation via CaMKII signaling

A Schematic of the signaling pathway by which MAP binds to CaMKII α, leading to the upregulation of CaMKII/ERK1/2/CREB/C-FOS signaling, promoting osteogenic differentiation and proliferation of SSPCs and protection against osteoporosis. AbstractDysregulation of bone homeostasis is closely related to the pathogenesis of osteoporosis. Suppressing bone resorption by osteoclasts to attenuate bone loss has been widely investigated, but far less effort has been poured toward promoting bone formation by osteoblasts. Here, we aimed to explore magnesium ascorbyl phosphate (MAP), a hydrophilic and stable ascorbic acid derivative, as a potential treatment option for bone loss disorder by boosting osteoblastogenesis and bone formation. We found that MAP could promote the proliferation and osteoblastic differentiation of human skeletal stem and progenitor cells (SSPCs)in vitro. Moreover, MAP supplementation by gavage could alleviate bone loss and accelerate bone defect healing through promoting bone formation. Mechanistically, we identified Calcium/calmodulin-dependent serine/threonine kinase II α (CaMKIIα) as the target of MAP, which was found to be directly bound and activated by MAP, then with a concomitant activation in the phosphorylation of ERK1/2 (Extracellular regulated kinase 1/2) and CREB (cAMP-response element binding protein) as well as an elevation of C-FOS expression. Furthe r, blocking CaMKII signaling notably abolished these effects of MAP on SSPCs and bone remodeling. ...

Source: Journal of Bone and Mineral Research - May 3, 2023 Category: Orthopaedics Authors: Yongheng Xie, Zhiteng Bao, Zhenmin Wang, Danfeng Du, Gaoyang Chen, Chungeng Liu, Hongyu Wang, Naibo Feng, Xiao Xiao, Song Wang, Xin Zhang, Yong Zhu, Zhengbin Yuan, Houqing Long, Dazhi Yang, Songlin Peng Tags: Research Article Source Type: research