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Abstract
BackgroundCurcumin can inhibit the osteoclastogenesis and the migration of several cells including macrophages. Osteoclast precursors (OCPs) are known to exist as bone marrow-derived macrophages (BMMs). This study aims to explore whether curcumin can prevent the fusion and differentiation of OCPs to mature osteoclasts by inhibiting OCP migration.MethodsIn this study, we investigated the role of curcumin in regulating the production of several chemokines (CCL2, CCL3 and CX3CL1) and the migration of OCPs by ELISA, Western blotting and Transwell assays. Furthermore, we explored the role of curcumin in the chemokines-related osteoclastogenesis using pharmacological intervention and virus infection, and used ovariectomized (OVX) mice (osteoporosis model) to explore the effect of curcumin on the production of specific chemokine in vivo.ResultsThe results showed that curcumin significantly reduced the production of CCL3 in OCPs. Moreover, curcumin-inhibited the migration of OCPs was not affected by CCR1 (Receptor of CCL3) overexpression. Remarkably, curcumin-reduced osteoclastogenesis was significantly reversed by CCL3 addition, while CCR1 overexpression did not increase the osteoclastogenesis in the presence of curcumin. Furthermore, in vivo assays also showed that curcumin significantly reduced the production of CCL3 in OCPs in the trabecular bone of OVX mice.ConclusionsIn conclusion, curcumin prevents the migration of OCPs by reducing CCL3 production, ultimately inhibiting the formation of mature osteoclasts. Therefore, our study provides the clues for improving the clinical strategies of osteoporosis, dental implantation or orthodontic treatment.
Highlights
Curcumin can inhibit the osteoclastogenesis and the migration of several cells including macrophages
Western blotting assays showed that curcumin reduced the expression level of CCL3 in Osteoclast precursors (OCPs) at 25 μM in the presence of RANKL and at 10, 15 and 25 μM without RANKL (Fig. 1g, h)
The results showed that CCR1 overexpression increased osteoclast number, large osteoclast number and osteoclast size, there were no statistical differences between the CCR1overexpressed group and the control group in the presence of curcumin (Fig. 4a-d), supporting that CCR1 overexpression is invalid in enhancing the osteoclastogenesis as curcumin blocks CCL3 production
Summary
Curcumin can inhibit the osteoclastogenesis and the migration of several cells including macrophages. This study aims to explore whether curcumin can prevent the fusion and differentiation of OCPs to mature osteoclasts by inhibiting OCP migration. Curcumin has obvious effect in the treatment of osteoporosis, which is conductive to fracture healing, implant repair and orthodontic treatment [5,6,7]. Curcumin can significantly improve the bone mineral density of lumbar vertebrae in ovariectomized (OVX) rats [5]. Heo, Kim, et al reported that curcumin can prevent bone loss in OVX mice [12, 13]. Curcumin can inhibit the formation of mature osteoclasts, which is involved in its bone-protective effect [10,11,12,13,14]
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