Evidence map›Paper›PMID 39702131›Full record

ArticleBMC musculoskeletal disorders2024

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

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

Abstract read
In one paragraph

Article in BMC musculoskeletal disorders, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Recent Use of Hyaluronic Acid in Dental Medicine.Materials (Basel, Switzerland) · 2025
    Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Khangarid Tenger *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.
Keiichiro Komori *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.
Ami MaeharaDepartment 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.
Kyosuke MiyazakiNR Laboratory, 493-10 Komakidai Nagareyama, Chiba, 270-0113, Japan.
Eriko MarukawaDepartment 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.
Toshitaka YoshiiDepartment of Orthopaedic Surgery, 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.
Kunikazu TsujiDepartment of Orthopaedic Surgery, 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. tsuji.orj@tmd.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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-μCT). 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.

Indexed as

Hyaluronic AcidMice, Inbred C57BLOvariectomyAnimalsBone DensityBone ResorptionDisease Models, AnimalFemaleMiceMolecular WeightOsteoblastsOsteoclastsOsteogenesisOsteoporosisOsteoporosis, PostmenopausalRANK LigandHyaluronic AcidRANK LigandHyaluronic acidOsteoporosisOvariectomyReceptor activator of nuclear factor kappa-B ligand

Identifiers

PMID39702131
PMCPMC11660811

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.