高分子量透明质酸可减轻去卵巢诱导的小鼠骨质流失。

High molecular weight hyaluronic acid alleviates ovariectomy-induced bone loss in mice.

作者信息

Tenger Khangarid, Komori Keiichiro, Maehara Ami, Miyazaki Kyosuke, Marukawa Eriko, Yoshii Toshitaka, Tsuji Kunikazu

机构信息

Department of Regenerative and Reconstructive Dental Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Institute of Science Tokyo), 1-5-45 Yushima Bunkyo-Ku, Tokyo, 113-8519, Japan.

Department of Nano-Bioscience, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Institute of Science Tokyo), 1-5-45 Yushima Bunkyo-Ku, Tokyo, 113-8519, Japan.

出版信息

BMC Musculoskelet Disord. 2024 Dec 19;25(1):1048. doi: 10.1186/s12891-024-08161-y.

DOI:10.1186/s12891-024-08161-y

PMID:39702131

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11660811/

Abstract

BACKGROUND

The rapid decline in ovarian function associated with menopause promotes osteoclast differentiation and increases bone resorption, disrupting of bone homeostasis and increasing the risk of osteoporosis. Hyaluronic acid (HA) is a polysaccharide ubiquitously present in the connective tissues. Recent reports indicate that high-molecular-weight HA (HMW-HA) promotes osteoblast proliferation, enhances alkaline phosphatase activity and mineral deposition, and promotes the expression of bone differentiation markers, such as Runx2 and osteocalcin. HMW-HA also inhibits the expression of the receptor activator of nuclear factor kappa-B ligand (RANKL) in osteoblasts. These results suggest that HMW-HA may be an effective therapeutic agent against postmenopausal osteoporosis. Therefore, this study aimed to examine whether HMW-HA alleviates ovariectomy (OVX)-induced bone loss in mice.

METHODS

Eight-week-old female C57BL/6 J mice were randomly divided into the following five groups: Group 1: Sham/saline, Group 2: OVX/saline, Group 3: OVX/HMW-HA [15 mg/kg]; Group 4: OVX/HMW-HA [30 mg/kg]; and Group 5: OVX/HMW-HA [60 mg/kg]. Mice were administered HMW-HA or saline subcutaneously starting from 1 week after OVX and changes in bone mass were analyzed at 5 weeks using three-dimensional micro-computed tomography (3D-μCT). In addition, changes in osteoclast parameters were analyzed histologically.

RESULTS

The reduction in trabecular bone volume and trabecular number was significantly ameliorated in the OVX/HMW-HA group compared with that observed in the OVX/saline group, along with a significant inhibition of the increase in trabecular spacing. In addition, the OVX/HMW-HA group exhibited a significant reduction in osteoclast surface area and number compared with the OVX/saline group, with no significant differences compared with the sham group. In vitro experiments revealed that depletion of HMW-HA from the culture medium by hyaluronidase treatment increased RANKL expression in the bone marrow stromal cell line ST2. These data suggest that HMW-HA alleviates OVX-induced bone loss by downregulating osteoclast formation and/or activity in mice.

CONCLUSION

HMW-HA is a potential novel therapeutic agent for osteoporosis.

摘要

背景

与更年期相关的卵巢功能快速衰退会促进破骨细胞分化并增加骨吸收，破坏骨稳态并增加骨质疏松症的风险。透明质酸（HA）是一种普遍存在于结缔组织中的多糖。最近的报告表明，高分子量HA（HMW-HA）可促进成骨细胞增殖，增强碱性磷酸酶活性和矿物质沉积，并促进骨分化标志物（如Runx2和骨钙素）的表达。HMW-HA还可抑制成骨细胞中核因子κB受体激活剂配体（RANKL）的表达。这些结果表明，HMW-HA可能是治疗绝经后骨质疏松症的有效药物。因此，本研究旨在探讨HMW-HA是否能减轻去卵巢（OVX）诱导的小鼠骨质流失。

方法

将8周龄雌性C57BL/6 J小鼠随机分为以下五组：第1组：假手术/生理盐水组；第2组：OVX/生理盐水组；第3组：OVX/HMW-HA [15 mg/kg]组；第4组：OVX/HMW-HA [30 mg/kg]组；第5组：OVX/HMW-HA [60 mg/kg]组。从OVX后1周开始，小鼠皮下注射HMW-HA或生理盐水，并在5周时使用三维微计算机断层扫描（3D-μCT）分析骨量变化。此外，通过组织学分析破骨细胞参数的变化。

结果

与OVX/生理盐水组相比，OVX/HMW-HA组的小梁骨体积和小梁数量减少明显改善，同时小梁间距增加受到显著抑制。此外，与OVX/生理盐水组相比，OVX/HMW-HA组的破骨细胞表面积和数量显著减少，与假手术组相比无显著差异。体外实验表明，用透明质酸酶处理培养基耗尽HMW-HA会增加骨髓基质细胞系ST2中RANKL的表达。这些数据表明，HMW-HA通过下调小鼠破骨细胞的形成和/或活性来减轻OVX诱导的骨质流失。