Magnesium Ascorbyl Phosphate Promotes Bone Formation Via CaMKII Signaling

Xie, Yongheng1,2; Bao, Zhiteng1,2; Wang, Zhenmin1,2; Du, Danfeng2; Chen, Gaoyang2,3; Liu, Chungeng1,2; Wang, Hongyu1,2; Feng, Naibo1,2; Xiao, Xiao1,2; Wang, Song1,2; Zhang, Xin1,2; Zhu, Yong1,2; Yuan, Zhengbin1,2; Long, Houqing1,2; Yang, Dazhi1,2; Peng, Songlin1,2,4

2023-05-01

10.1002/jbmr.4820

JOURNAL OF BONE AND MINERAL RESEARCH   影响因子和分区

0884-0431

1523-4681

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 IIa (CaMKIIa) 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. (c) 2023 American Society for Bone and Mineral Research (ASBMR).

MAP STEM CELLS BONE FORMATION CAMKII OSTEOPOROSIS

SCI

英语

第一 ; 通讯

National Natural Science Foundation of China["82272488","82272458"] ; Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration[ZDSYS20200811143752005] ; Sanming Project of Medicine in Shenzhen[SZSM202111015] ; Shenzhen Municipal Science and Technology Innovation Committee Project[JCYJ20220530152812028]

Endocrinology & Metabolism

Endocrinology & Metabolism

WOS:000998423200001

WILEY

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Southern Univ Sci & Technol, Jinan Univ, Affiliated Hosp 1, Dept Orthoped Surg,Clin Med Coll 2,Shenzhen People, Shenzhen 518020, Peoples R China
2.Shenzhen Key Lab Musculoskeletal Tissue Reconstruc, Shenzhen, Peoples R China
3.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp, Div Hand Surg,Dept Orthoped Surg,Clin Med Coll 2,A, Shenzhen, Peoples R China
4.Shenzhen Peoples Hosp, Shenzhen Clin Res Ctr Geriatr, Shenzhen, Peoples R China

Xie, Yongheng,Bao, Zhiteng,Wang, Zhenmin,et al. Magnesium Ascorbyl Phosphate Promotes Bone Formation Via CaMKII Signaling[J]. JOURNAL OF BONE AND MINERAL RESEARCH,2023,38(7).

Xie, Yongheng.,Bao, Zhiteng.,Wang, Zhenmin.,Du, Danfeng.,Chen, Gaoyang.,...&Peng, Songlin.(2023).Magnesium Ascorbyl Phosphate Promotes Bone Formation Via CaMKII Signaling.JOURNAL OF BONE AND MINERAL RESEARCH,38(7).

Xie, Yongheng,et al."Magnesium Ascorbyl Phosphate Promotes Bone Formation Via CaMKII Signaling".JOURNAL OF BONE AND MINERAL RESEARCH 38.7(2023).