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

被引：0

作者：

Tenger, Khangarid ^{[1
]}

Komori, Keiichiro ^{[2
]}

Maehara, Ami ^{[2
]}

Miyazaki, Kyosuke ^{[3
]}

Marukawa, Eriko ^{[1
,4
]}

Yoshii, Toshitaka ^{[5
]}

Tsuji, Kunikazu ^{[5
]}

机构：

[1] Tokyo Med & Dent Univ, Inst Sci Tokyo, Grad Sch Med & Dent Sci, Dept Regenerat & Reconstruct Dent Med, 1-5-45 Yushima,Bunkyo Ku, Tokyo 1138519, Japan

[2] Tokyo Med & Dent Univ, Inst Sci Tokyo, Grad Sch Med & Dent Sci, Dept Nanobiosci, 1-5-45 Yushima,Bunkyo Ku, Tokyo 1138519, Japan

[3] NR Lab, 493-10 Komakidai, Nagareyama, Chiba 2700113, Japan

[4] Tokyo Med & Dent Univ Hosp, Inst Sci Tokyo Hosp, Dent Implant Clin, Bunkyo Ku, 1-5-45 Yushima,Bunkyo Ku, Tokyo 1138519, Japan

[5] Tokyo Med & Dent Univ, Inst Sci Tokyo, Grad Sch Med & Dent Sci, Dept Orthopaed Surg, 1-5-45 Yushima,Bunkyo Ku, Tokyo 1138519, Japan

来源：

BMC MUSCULOSKELETAL DISORDERS | 2024年 / 25卷 / 01期

基金：

日本学术振兴会;

关键词：

Hyaluronic acid; Osteoporosis; Ovariectomy; Receptor activator of nuclear factor kappa-B ligand; OSTEOCYTE REGULATION; RECEPTOR ACTIVATOR; MINERAL DENSITY; OSTEOPOROSIS; MECHANISM; MODEL; DIFFERENTIATION; EXPRESSION; GUIDELINES; SKELETAL;

D O I：

10.1186/s12891-024-08161-y

中图分类号：

R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学（修复外科学）];

学科分类号：

摘要：

BackgroundThe 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.MethodsEight-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-mu CT). In addition, changes in osteoclast parameters were analyzed histologically.ResultsThe 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.ConclusionHMW-HA is a potential novel therapeutic agent for osteoporosis.

引用

页数：13

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