Department of Orthopaedic Surgery, Sapporo Medical University, Sapporo, Japan.
Second Department of Anatomy, Sapporo Medical University, Sapporo, Japan.
Sci Rep. 2018 Jan 18;8(1):1161. doi: 10.1038/s41598-018-19516-6.
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the most valuable source of autologous cells for transplantation and tissue regeneration to treat osteoporosis. Although BM-MSCs are the primary cells responsible for maintaining bone metabolism and homeostasis, their regenerative ability may be attenuated in postmenopausal osteoporosis patients. Therefore, we first examined potential abnormalities of BM-MSCs in an oestrogen-deficient rat model constructed by ovariectomy (OVX-MSCs). Cell proliferation, mobilisation, and regulation of osteoclasts were downregulated in OVX-MSCs. Moreover, therapeutic effects of OVX-MSCs were decreased in OVX rats. Accordingly, we developed a new activator for BM-MSCs using human umbilical cord extracts, Wharton's jelly extract supernatant (WJS), which improved cell proliferation, mobilisation and suppressive effects on activated osteoclasts in OVX-MSCs. Bone volume, RANK and TRACP expression of osteoclasts, as well as proinflammatory cytokine expression in bone tissues, were ameliorated by OVX-MSCs activated with WJS (OVX-MSCs-WJ) in OVX rats. Fusion and bone resorption activity of osteoclasts were suppressed in macrophage-induced and primary mouse bone marrow cell-induced osteoclasts via suppression of osteoclast-specific genes, such as Nfatc1, Clcn7, Atp6i and Dc-stamp, by co-culture with OVX-MSCs-WJ in vitro. In this study, we developed a new activator, WJS, which improved the functional abnormalities and therapeutic effects of BM-MSCs on postmenopausal osteoporosis.
骨髓间充质干细胞（BM-MSCs）是自体细胞移植和组织再生治疗骨质疏松症最有价值的来源。尽管 BM-MSCs 是负责维持骨代谢和内稳态的主要细胞，但在绝经后骨质疏松症患者中，其再生能力可能会减弱。因此，我们首先在去卵巢（OVX）大鼠模型中检查了雌激素缺乏导致的 BM-MSCs 潜在异常。OVX-MSCs 中的细胞增殖、动员和破骨细胞调节能力下降。此外，OVX 大鼠中 OVX-MSCs 的治疗效果也降低了。因此，我们使用人脐带提取物 Wharton's jelly 提取上清液（WJS）开发了一种新的 BM-MSCs 激活剂，该激活剂改善了 OVX-MSCs 中的细胞增殖、动员和对激活的破骨细胞的抑制作用。WJS 激活的 OVX-MSCs（OVX-MSCs-WJ）在 OVX 大鼠中改善了骨量、破骨细胞的 RANK 和 TRACP 表达以及骨组织中的促炎细胞因子表达。通过抑制破骨细胞特异性基因（如 Nfatc1、Clcn7、Atp6i 和 Dc-stamp），体外与 OVX-MSCs-WJ 共培养可抑制巨噬细胞诱导和原代小鼠骨髓细胞诱导的破骨细胞的融合和骨吸收活性。在这项研究中，我们开发了一种新的激活剂 WJS，它改善了 BM-MSCs 对绝经后骨质疏松症的功能异常和治疗效果。
