Department II of Gastroenterology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
Mol Med Rep. 2018 Jun;17(6):7947-7951. doi: 10.3892/mmr.2018.8835. Epub 2018 Mar 29.
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.
核因子-κB 受体激活剂配体 (RANKL) 是肿瘤坏死因子受体配体家族的成员，是参与破骨细胞分化的关键因子。藏红花素是藏红花 L. 的一种药理活性成分，据报道可减轻去卵巢大鼠的骨质疏松症。然而，藏红花素对破骨细胞形成的影响的分子机制仍有待确定。本研究旨在探讨藏红花素对 RANKL 诱导的破骨细胞生成的影响及其潜在的分子机制。结果表明，藏红花素可减少骨髓来源的巨噬细胞 (BMM) 中的破骨细胞生成。此外，藏红花素下调破骨细胞标志物蛋白的表达。在机制上，藏红花素通过抑制 IκBα 的降解和防止 NF-κB p65 亚基核转位，以及在 BMM 中激活 c-Jun N-末端激酶 (JNK)，抑制 RANKL 诱导的核因子-κB (NF-κB) 激活。综上所述，本研究结果表明，藏红花素通过抑制 JNK 和 NF-κB 信号通路下调破骨细胞分化。因此，藏红花素可能是治疗破骨细胞相关疾病（包括骨质疏松症）的潜在治疗剂。
