Targeting p38 MAPK: A potential bridge between ER stress and age-related bone loss

Abstract

The endoplasmic reticulum (ER) is crucial in the development of numerous age-related bone disorders. Notably, ER stress can precipitate bone loss by orchestrating inflammatory responses, apoptosis, and autophagy through the activation of the p38 MAPK pathway. Age-related bone loss diseases pose a significant burden on society and healthcare as the global population ages. This review provides a comprehensive analysis of recent research advancements, delving into the critical role of ER stress-activated p38 MAPK in inflammation, apoptosis, and autophagy, as well as its impact on bone formation and bone resorption. This review elucidates the molecular mechanisms underlying the involvement of ER stress-activated p38 MAPK in osteoporosis, rheumatoid arthritis, periodontitis, and osteoarthritis and discusses the therapeutic potential of targeting p38 MAPK. Furthermore, this review provides a scientific foundation for new therapeutic strategies by highlighting prospective research directions.