Proper mechanical stress promotes femoral head recovery from steroid-induced osteonecrosis in rats through the OPG/RANK/RANKL system

Abstract

Background: Long-term use of steroid may lead to osteonecrosis of the femoral head (ONFH). Mechanical stress may help bone formation and remodeling. This study aimed to probe the role of mechanical stress in the femoral head recovery in rats. Methods: Rat models with ONFH were induced by steroid. Rats were subjected to different levels of mechanical stress (weight-bearing training), and then the morphology and bone density of femoral head of rats were measured. The mRNA and protein levels of the OPG/RANK/RANKL axis in rat femoral head were assessed. Gain-and loss-of function experiments of OPG were performed to identify its role in femoral head recovery following stress implement. The ex vivo cells were extracted and the effects of stress and OPG on osteogenesis in vitro were explored. Results: Steroid-induced ONFH rats showed decreased bone density and increased bone spaces, as well as necrotic cell colonies and many cavities in the cortical bones and trabeculars. Proper mechanical stress or upregulation of OPG led to decreased RANK/RANKL expression and promoted femoral head recovery from steroid-induced osteonecrosis. However, excessive mechanical stress might impose too much load on the femurs thus leading even retard femoral head recovery process. In addition, the in vitro experimental results supported that proper stress and overexpression of OPG increased the osteogenesis of ex vivo cells of femoral head. Conclusion: This study provided evidence that proper mechanical stress promoted femoral head recovery from steroid-induced osteonecrosis through the OPG/RANK/RANKL system, while overload might inhibit the recovery process. This study may offer novel insights for ONFH treatment.

Acupotomy Contributes to Suppressing Subchondral Bone Resorption in KOA Rabbits by Regulating the OPG/RANKL Signaling Pathway

“…As reported previously in numerous studies, OPG/RANKL is a mechanically sensitive signaling pathway [58,59]. Benign mechanical stimulation can increase the OPG/RANKL ratio in KOA subchondral bone, which effectively inhibits osteoclast activity and bone resorption [60]. Our previous studies [21] have confirmed that acupotomy intervention activates the FAK-PI3K mechanical pathway to relieve KOA cartilage degeneration by correcting abnormal mechanical stress.…”

Inhibition of miR‐93‐5p promotes osteogenic differentiation in a rabbit model of trauma‐induced osteonecrosis of the femoral head

“…Fu et al . found that proper mechanical stress could promote osteonecrosis recovery via the OPG/RANK/RANKL system [ 40 ]. These studies emphasized that OPG and RANKL might be potential therapeutic targets for ONFH.…”

IL-34 Aggravates Steroid-Induced Osteonecrosis of the Femoral Head via Promoting Osteoclast Differentiation

“…On the other hand, intensification of therapy with steroid administration can lead to steroid-induced ONFH, which is a common iatrogenic complication in autoimmune disease and severe acute respiratory syndrome treatment ( 8 9 10 ). Enhanced reactive oxygen species production, altered mechanical stress, dysregulated autophagy, and increased inflammatory response are considered to contribute to the development of ONFH ( 4 11 12 13 ).…”