Crocin inhibits RANKL‑induced osteoclastogenesis by regulating JNK and NF‑κB signaling pathways.

Receptor activator of nuclear factor‑κB ligand (RANKL), a member of the tumor necrosis factor receptor-ligand family, is a crucial factor involved in osteoclast differentiation. Crocin, a pharmacologically active component of Crocus sativus L., has been reported to attenuate ovariectomy‑induced osteoporosis in rats. However, the molecular mechanism underlying the effect of crocin on osteoclast formation remains to be determined. The present study aimed to investigate the effect of crocin on RANKL‑induced osteoclastogenesis and its underlying molecular mechanism. Results demonstrated that crocin decreased osteoclastogenesis in bone marrow‑derived macrophages (BMMs). In addition, the expression levels of osteoclast marker proteins were downregulated by crocin. Mechanistically, crocin inhibited RANKL‑induced activation of nuclear factor‑κB (NF‑κB) by suppressing inhibitor of κBα degradation and preventing NF‑κB p65 subunit nuclear translocation, and by activating c‑Jun N‑terminal kinase (JNK) in BMMs. In summary, the results of the present study suggested that crocin downregulates osteoclast differentiation via inhibition of JNK and NF‑κB signaling pathways. Thus, crocin may be a potential therapeutic agent for the treatment of osteoclast‑associated diseases, including osteoporosis.