title: Curcumin alleviates glucocorticoid-induced osteoporosis by protecting osteoblasts from apoptosis in vivo and in vitro.
abstract: Curcumin, an active component of the rhizomes of Curcumin longa L., possesses broad anti-inflammation and anti-cancer properties. Curcumin was previously reported to be capable of protecting ovariectomized rats against osteoporosis. However, the effect of curcumin on glucocorticoid-induced osteoporosis (GIO) is not yet clear. The present study investigated the effects of curcumin on dexamethasone (Dex)-induced osteoporosis in vivo and Dex-induced osteoblast apoptosis in vivo and in vitro. The GIO rat model was induced by subcutaneous injection of Dex for 60 days and verified to be successful as evidenced by the significantly decreased bone mineral density (BMD) determined using dual X-ray absorptiometry. Subsequently, curcumin administration (100 mg/kg) for 60 days obviously increased BMD and bone-alkaline phosphatase, decreased carboxy-terminal collagen cross links, enhanced bone mechanical strength, and improved trabecular microstructure, thereby alleviating Dex-induced osteoporosis. Mechanically, curcumin remarkably reversed Dex-induced femoral osteoblast apoptosis in vivo. In cultured primary osteoblasts, pretreatment with curcumin concentration-dependently decreased the number of Dex-induced apoptotic osteoblasts by down-regulating the ratio of Bax/Bcl-2 as well as the levels of cleaved caspase-3 and cleaved poly ADP-ribose polymerase (PARP). Moreover, curcumin pretreatment activated extracellular signal regulated kinase (ERK) signalling in Dex-induced osteoblasts by up-regulating the expression level of p-ERK1/2. Taken together, our study demonstrated that curcumin could ameliorate GIO by protecting osteoblasts from apoptosis, which was possibly related to the activation of the ERK pathway. The results suggest that curcumin may be a promising drug for prevention and treatment of GIO.
authors.affiliation: Department of Spine and Joint Surgery, Shengjing Hospital of China Medical University, Shenyang, 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, 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, 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, China.
authors.forename: Gen
authors.initials: G
authors.lastname: Ba
authors.affiliation: Department of Spine and Joint Surgery, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Spine and Joint Surgery, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Fu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D019610:Cytoprotection / Q000187:drug effects*; D003907:Dexamethasone / Q000009:adverse effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000009:adverse effects*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D010024:Osteoporosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D048049:Extracellular Signal-Regulated MAP Kinases; D003474:Curcumin
keywords: apoptosis; curcumin; extracellular signal regulated kinase (ERK); glucocorticoid-induced osteoporosis (GIO); osteoblast