Supplemental magnesium gluconate recovers osteoblastic Wntless ablation-induced degenerative bone complications

Introduction: Although numerous studies have highlighted the involvement of Wnt-mediated signaling in Mg ion-enhanced bone healing, whether Wnt-stimulated signaling is essential for the Mg ion-triggered bone repair and mass accrual is not yet completely understood. Materials and methods: We generated Wls^fl/fl wild-type (WT) control and their corresponding mutant (MT), Col2.3-Cre;Wls^fl/fl mice of osteoblastic Wntless (Wls) ablation and explored how supplemental magnesium gluconate (MgG) affects bone mass accrual and defected bone healing in relation to the Wls ablation. Results: Osteoblastic Wls ablation impaired bone mass accrual and bone healing along with age-related degenerative complications in bone marrow (BM) and BM cells. Oral supplementation of WT mice with MgG did not change natural bone mass accrual, but enhanced regenerative bone healing in femoral defects and the functionalities of BM cells. Supplemental MgG suppressed the Wls ablation-related bone loss and also stimulated new bone formation in the defects of MT mice. The MgG-induced beneficial effects in the MT mice were orchestrated with its potencies to ameliorate senescence, oxidative damage, and functional loss of BM and BM adherent cells, as well as to stimulate osteogenic activity. Conclusion: This study demonstrates that supplemental MgG is able to improve bone homeostatic maintenance by recovering age-related degenerative complications even at the lack of osteoblastic Wnt-stimulated signaling.