Propofol attenuates osteoclastogenesis by lowering RANKL/OPG ratio in mouse osteoblasts

Abstract

Bone remodeling plays an important role in the bone healing process; for example, following fracture. The relative ratio of the receptor activator of nuclear factor kappa B ligand (RANKL)/ osteoprotegerin (OPG) controls osteoclast differentiation, thereby playing a pivotal role in the regulation of bone remodeling. Propofol, a widely used anesthetic agent in orthopedic procedures, is considered to possess potential antioxidant properties owing to its structural similarity to α-tocopherol. Antioxidants are known to enhance bone healing. Accordingly, in the present study, we aimed to investigate osteoblastic differentiation and RANKL/OPG expression following propofol administration, in order to assess the potentially beneficial effects of this drug on the bone remodeling process, using calvarial primary osteoblasts from newborn mice. Calvarial pre-osteoblast cells were cultured in media containing clinically relevant concentrations of propofol, and cytotoxicity, effects on cell proliferation, osteogenic activity, and osteoclastogenesis were examined. The present findings indicated that propofol did not exert cytotoxic effects or alter cell proliferation in primary calvarial osteoblasts. Further, propofol did not affect osteoblast differentiation. The RANKL/OPG ratio was found to be decreased following propofol administration, and osteoclastogenesis was significantly reduced, indicating that propofol attenuated the osteoclastogenesis-supporting activity of osteoblasts. The results demonstrate that propofol, at clinically relevant concentrations, exerts beneficial effects on bone remodeling by attenuating osteoclastogenesis via suppression of the RANKL/OPG expression axis.

Electrical therapies act on the Ca2+/CaM signaling pathway to enhance bone regeneration with bioactive glass [S53P4] and allogeneic grafts

“…Under homeostatic conditions, RANKL and OPG expression are balanced. The relative proportion of RANKL/OPG controls the differentiation of osteoclasts, thus playing a central role in the regulation of bone remodeling 50. The RANKL/OPG ratio observed in our study, especially for ES-stimulated groups, favorably modulated the bone remodeling process, which was also demonstrated by TRAP-positive cells.…”

Effects of the Bone/Bone Marrow Microenvironments on Prostate Cancer Cells and CD59 Expression

“…This result was also verified by immunofluorescence analysis, suggesting that there may be interactions between the bone/bone marrow microenvironment and prostate cancer cells in vivo. Although we found that hBMSC and hFOB1.19 cells also enhanced the expression of OPG in PC3 cells, activation or inhibition of the RANK/-RANKL signaling pathway depends on the ratio of RANKL to OPG in the microenvironment [38,39], i.e., if the increase in RANKL expression is greater than that of OPG, the RANK/RANKL signaling pathway will still be activated. Thus, an increase in OPG expression and the activation of the RANK/RANKL signaling pathway are not necessarily contradictory.…”

Biological Mechanisms of Paeonoside in the Differentiation of Pre-Osteoblasts and the Formation of Mineralized Nodules

“…In addition, osteoblasts mainly synthesize oteoprotegerin (OPG) as a circulating decoy receptor of RANKL [61]. The soluble RANKL/OPG system controls the differentiation and function of osteoclasts, thereby clinically determining bone status [62]. Growing evidence suggests that epigenetic modification plays a critical role in the formation of normal bone and the pathogenesis of bone diseases [63].…”