Osteoporosis remission via an anti-inflammaging effect by icariin activated autophagy

The pace of bone formation slows down with aging, which leads to the development of osteoporosis. In addition to senescent bone marrow mesenchymal stem cells (S-BMSCs), senescent macrophages (S-MΦs) present in the bone marrow produce numerous inflammatory cytokines that contribute to the inflammaged microenvironment and are involved in the development of osteoporosis. Although autophagy activation has shown a significant anti-aging effect, its influence on inflammaging and its role in osteoporosis treatment remain unclear. Traditional Chinese herbal medicine contains bioactive components that exhibit remarkable advantages in bone regeneration. We have demonstrated that icariin (ICA), a bioactive component of traditional Chinese herbal medicine, activates autophagy, exerts a significant anti-inflammaging effect on S-MΦs, and rejuvenates osteogenesis of S-BMSCs, thereby alleviating bone loss in osteoporotic mice. The transcriptomic analysis further reveals that the TNF-α signaling pathway, which is significantly associated with the level of autophagy, regulates this effect. Moreover, the expression of senescence-associated secretory phenotype (SASP) is significantly reduced after ICA treatment. In summary, our findings suggest that bioactive components/materials targeting autophagy can effectively modulate the inflammaging of S-MΦs, offering an innovative treatment strategy for osteoporosis remission and various age-related comorbidities.