title: ST1926 Attenuates Steroid-Induced Osteoporosis in Rats by Inhibiting Inflammation Response.
abstract: Steroid, also known as glucocorticoid, induced osteonecrosis of the femoral head in young adults, which has been a challenging disorder for the frequent incidence of collapse of femoral head, leading to dysfunction of hip joint and impairing life quality of human. Bioavailable and less toxic synthetic retinoids, such as the atypical adamantyl retinoid ST1926, have been developed and investigated in clinical trials for many diseases. Serum lipid-related indicators were assessed to elucidate the role of ST1926 in regulating lipid metabolism. Microfocal computed tomography (Micro-CT) was included to explore the effects of ST1926 treatment on microstructure and bone mass. Then, the role of ST1926 treatment in regulating osteoclast differentiation was also evaluated in vivo and in vitro. In addition, alkaline phosphatase (ALP), osteoprotegerin (OPG), bone alkaline phosphatase (BAP) and bone morphogenic protein (BMP) expression in serum and cells were detected at protein or mRNA levels. The ratio of empty lacuna in the bone tissue samples was significantly low in ST1926-treated groups than in the control group. Micro-CT evaluation suggested that ST1926 treatment could ameliorate the microstructure of the bone and up-regulate bone mineral density in steroid-induced rats. Moreover, ST1926 treatment suppressed osteoclast differentiation and promoted bone formation markers. Also, OPG, ALP, and Wnt3a/β-catenin down-regulation as well as inflammation up-regulation could be reversed by ST1926 administration through NFκB inhibition. Hence, ST1926 may inhibit steroid-induced osteoporosis and promote steroid-induced bone remodeling by regulating the Wnt3a/β-catenin/NFκB signaling pathway. J. Cell. Biochem. 118: 2072-2086, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Xinxiang Medical University, Weihui City, Henan, 453100, China.
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Xinxiang Medical University, Weihui City, Henan, 453100, China.
authors.forename: Yuan-Xia
authors.initials: YX
authors.lastname: Huang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Xinxiang Medical University, Weihui City, Henan, 453100, China.
authors.forename: Jin-Gang
authors.initials: JG
authors.lastname: Tao
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D001862:Bone Resorption / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D002934:Cinnamates / Q000494:pharmacology*; D005786:Gene Expression Regulation; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects / Q000031:analogs & derivatives; D000077555:Methylprednisolone Acetate; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010020:Osteonecrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C472791:3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid; D050071:Bone Density Conservation Agents; D019485:Bone Morphogenetic Proteins; D002934:Cinnamates; C495268:Ctnnb1 protein, rat; D016328:NF-kappa B; D053244:Osteoprotegerin; C506032:Tnfrsf11b protein, rat; D060509:Wnt3A Protein; D051176:beta Catenin; D000077555:Methylprednisolone Acetate; D000469:Alkaline Phosphatase; D000218:Adamantane; D008775:Methylprednisolone
keywords: NF-κB; OSTEONECROSIS; ST1926; STEROID; Wnt3a/β-CATENIN