Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518035, China; Department of Interventional Radiology and Vascular Surgery, Peking University First Hospital, Beijing, 100034, China.
Department of Oncology Rehabilitation, Shenzhen Luohu People's Hospital, The Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, 518001, PR China.
Biochem Biophys Res Commun. 2021 May 21;554:33-40. doi: 10.1016/j.bbrc.2021.02.100. Epub 2021 Mar 25.
Glucocorticoid-induced osteoporosis (GIOP) has emerged as a challenge after long-term glucocorticoid administration during the clinical therapy of diverse diseases. Although some candidates for GIOP treatment have been explored, there is still a lack of reliable drugs for GIOP prevention. In this study, rat bone marrow stem cells (rBMSCs) were utilized to investigate the feasibility of applying strontium gluconate (GluSr), which displays mild activity, easy absorption and good biocompatibility, for GIOP prevention. Thirty-two SD rats were divided into 4 groups to explore the effects of GluSr on osteoporosis rescue in vivo. Our results suggested that GluSr markedly alleviated dexamethasone (DEX)-induced apoptosis of osteoblast precursor cells and rBMSCs and enhanced rBMSC osteogenesis differentiation in vitro. GluSr also effectively promoted osteoblast survival, inhibited osteoclast differentiation and restored bone formation in GIOP rat models. Microarray analysis of the femora from GIOP rats treated with GluSr revealed that the signalling pathways of the glucocorticoid receptor (GR), oestrogen receptor gene (ESR) and vitamin D receptor (VDR) were involved in bone restoration by GluSr. In summary, our study proved that GluSr enhanced osteoblast differentiation and suppressed osteoclast activity both in vitro and in vivo. GluSr might function as a novel strontium reagent for GIOP prevention.
糖皮质激素诱导的骨质疏松症（GIOP）在多种疾病的临床治疗中长期应用糖皮质激素后成为一个挑战。虽然已经探索了一些用于治疗 GIOP 的候选药物，但仍然缺乏用于预防 GIOP 的可靠药物。在这项研究中，利用大鼠骨髓基质细胞（rBMSCs）研究了葡萄糖酸锶（GluSr）在预防 GIOP 中的应用的可行性，葡萄糖酸锶具有温和的活性、易吸收和良好的生物相容性。将 32 只 SD 大鼠分为 4 组，以探讨 GluSr 在体内对骨质疏松症的治疗作用。我们的结果表明，GluSr 显著减轻了地塞米松（DEX）诱导的成骨细胞前体细胞和 rBMSCs 的凋亡，并增强了 rBMSC 的成骨分化。GluSr 还能有效促进成骨细胞的存活，抑制破骨细胞的分化，并恢复 GIOP 大鼠模型中的骨形成。对经 GluSr 治疗的 GIOP 大鼠的股骨进行的微阵列分析表明，葡萄糖酸锶通过糖皮质激素受体（GR）、雌激素受体基因（ESR）和维生素 D 受体（VDR）信号通路参与骨修复。总之，我们的研究证明了 GluSr 能增强体外和体内成骨细胞的分化和抑制破骨细胞的活性。GluSr 可能是一种预防 GIOP 的新型锶试剂。
