Magnesium Ascorbyl Phosphate Promotes Bone Formation Via CaMKII Signaling

Abstract

Dysregulation 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 IIα (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. Further, blocking CaMKII signaling notably abolished these effects of MAP on SSPCs and bone remodeling. Taken together, our data indicated that MAP played an important role in enhancing bone formation through the activation of CaMKII/ERK1/2/CREB/C‐FOS signaling pathway and may be used as a novel therapeutic option for bone loss disorders such as osteoporosis. © 2023 American Society for Bone and Mineral Research (ASBMR).

Ghrelin enhances tubular magnesium absorption in the kidney

“…The vast majority of total body Mg 2+ is stored in bone ( Alfrey et al, 1974 ; de Baaij et al, 2015 ). Mg 2+ is involved with bone metabolism by inducing osteoblast proliferation ( Xie et al, 2023 ). Mg 2+ -deficient animals have impaired bone growth, decreased bone strength, decreased osteoblasts, and increased osteoclast numbers ( Boskey et al, 1992 ; Rude et al, 2003 ; Rude and Gruber, 2004 ).…”