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.

Excessive Activation of TLR4/NF-κB Interactively Suppresses the Canonical Wnt/β-catenin Pathway and Induces SANFH in SD Rats

“…Liu 44 further demonstrated in a mouse orthopedic study that a singleton therapeutic agent for osteoporosis can gain a coupled effect on the stimulation of bone formation by the Wnt/GSK3β/β-catenin pathway and on the suppression of bone resorption by the NF-κB/c-fos/NFATc1 pathway. The most recent result of Zhao 45 directly indicated that inhibiting NF-κB down regulates inflammatory cytokine release, enhances osteoblast differentiation, and stimulates the Wnt3a/β-catenin pathway; these results agree with the present one.…”

Calycosin modulates inflammation via suppressing TLR4/NF‐κB pathway and promotes bone formation to ameliorate glucocorticoid‐induced osteonecrosis of the femoral head in rat

“…Single use of high-dose MPS to induce ONFH has been popularly employed as the method to establish the animal model. Many researchers reported that the GC-induced ONFH could be duplicated in this model, and the pathological characteristics of osteonecrosis in rat were similar to human's (Takeda, Kaisho, & Akira, 2003;H. X. Zhao, Huang, & Tao, 2017).…”

Arbutin ameliorates glucocorticoid-induced osteoporosis through activating autophagy in osteoblasts

“…38 Treatment of atypical adamantyl retinoid ST1926 increases ALP level and reduces TRAP positive cells, which attenuates bone loss in the femoral head of steroid-induced rats with osteoporosis. 39 To date, there is no research to investigate the role of arbutin in bone formation and bone resorption in glucocorticoid-induced osteoporosis. Our study revealed that arbutin treatment promoted bone formation (reflected by increased BMP2 and Runx2 expression, ALP activity, and osteocalcin level) and inhibited bone resorption (reflected by decreased CTX-1 level and TRAP activity) in Dex-induced osteoporotic mice.…”