Reference - Detail
| RRC ID | 82607 |
|---|---|
| Author | Tenger K, Komori K, Maehara A, Miyazaki K, Marukawa E, Yoshii T, Tsuji K. |
| Title | High molecular weight hyaluronic acid alleviates ovariectomy-induced bone loss in mice. |
| Journal | BMC Musculoskelet Disord |
| 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. |
| Volume | 25(1) |
| Pages | 1048 |
| Published | 2024-12-19 |
| DOI | 10.1186/s12891-024-08161-y |
| PII | 10.1186/s12891-024-08161-y |
| PMID | 39702131 |
| PMC | PMC11660811 |
| MeSH | Animals Bone Density / drug effects Bone Resorption / drug therapy Bone Resorption / prevention & control Disease Models, Animal Female Hyaluronic Acid* / pharmacology Mice Mice, Inbred C57BL* Molecular Weight Osteoblasts / drug effects Osteoclasts / drug effects Osteogenesis / drug effects Osteoporosis / diagnostic imaging Osteoporosis / drug therapy Osteoporosis, Postmenopausal / drug therapy Ovariectomy* / adverse effects RANK Ligand / metabolism X-Ray Microtomography |
| Resource | |
| Human and Animal Cells | ST2(RCB0224) |