title: Curcumin alleviates glucocorticoid-induced osteoporosis through the regulation of the Wnt signaling pathway.
abstract: It is known that prolonged glucocorticoid (GC) treatment results in osteoporosis. This study aimed to evaluate the protective effects of curcumin on the bones of rats with dexamethasone (DXM)-induced osteoporosis. In the present study, rats were administered DXM for 60 days to induce osteoporosis, and they were then treated with curcumin (100 mg/kg/day) for a further 60 days. H&E staining was used to observe the pathological changes in the femurs. Serum osteocalcin levels and collagen-type I fragments (CTX) were examined as bone metabolism markers. The results revealed that treatment with curcumin attenuated DXM-induced bone injury in femurs, increased the serum levels of osteocalcin and decreased the levels of CTX. In addition, in in vitro experiments, primary rat osteoblasts treated with curcumin at 0.5, 1 and 2 µM were exposed to 100 nM DXM. An MTT assay was used to determine the proliferative ability of the cells. Alkaline phosphatase activity, and the mRNA expression levels of runt‑related transcription factor 2 (Runx2), osterix, osteocalcin, collagen, type 1, alpha 1 (Col1A1) and osteonectin were detected to assess transcription factor-associated osteogenic differentiation. The mRNA and protein expression levels of osteoprotegerin (OPG) and receptor activator for nuclear factor-kappa B ligand (RANKL) were detected to assess cytokine-associated osteoclastogenesis. The results demonstrated that curcumin prevented the DXM-induced inhibition of the proliferative ability of the osteoblasts in a dose-dependent manner. In addition, curcumin upregulated the mRNA expression levels of transcription factors that favor osteoblast differentiation and increased the ratio of OPG to RANKL. Moreover, the effects of curcumin on the Wnt signaling pathway were also investigated. RT-qPCR and western blot analysis demonstrated that the Wnt signaling pathway, which was inhibited by DXM, was re-activated upon treatment with curcumin. Immunofluorescence staining revealed that curcumin restored the intranuclear staining of β-catenin in the DXM-stimulated osteoblasts. Collectively, our data demonstrate that curcumin may be a potential therapeutic agent for the treatment of GC-induced osteoporosis.
authors.affiliation: Department of Spine and Joint Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: The Seventh Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Jinqi
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Spine and Joint Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.affiliation: Department of Spine and Joint Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Mu
authors.affiliation: Department of Spine and Joint Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Fu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics; D003474:Curcumin / Q000008:administration & dosage*; D003907:Dexamethasone / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000009:adverse effects; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D015675:Osteocalcin / Q000096:biosynthesis / Q000235:genetics; D010024:Osteoporosis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D053244:Osteoprotegerin / Q000096:biosynthesis / Q000235:genetics*; D053245:RANK Ligand / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D005938:Glucocorticoids; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; C493717:Runx2 protein, rat; D015675:Osteocalcin; D003907:Dexamethasone; D003474:Curcumin