Evidence map›Paper›PMID 37076950›Full record

ArticleJournal of cachexia, sarcopenia and muscle2023

Ginkgolide B facilitates muscle regeneration via rejuvenating osteocalcin-mediated bone-to-muscle modulation in aged mice.

Belle Yu-Hsuan Wang, Yi-Fan Chen, Allen Wei-Ting Hsiao, Wan-Jing Chen, Chien-Wei Lee, Oscar Kuang-Sheng Lee

Open access · goldAbstract read
In one paragraph

Article in Journal of cachexia, sarcopenia and muscle, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% of its field
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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

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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

6 authors at 4 institutions in 3 countries.

Belle Yu-Hsuan WangMusculoskeletal Research Laboratory, SH Ho Scoliosis Research Laboratory, Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
Yi-Fan ChenThe Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.ORCID 0000-0002-0793-8769
Allen Wei-Ting HsiaoDepartment of Orthopaedics and Traumatology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.
Wan-Jing ChenThe Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Chien-Wei LeeCenter for Translational Genomics & Regenerative Medicine Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.ORCID 0000-0002-6679-0020
Oscar Kuang-Sheng LeeCenter for Translational Genomics & Regenerative Medicine Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.ORCID 0000-0001-5232-5374
Chinese University of Hong Kong · HKTaipei Medical University · TWChina Medical University · TWNational Yang Ming Chiao Tung University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe progressive deterioration of tissue-tissue crosstalk with aging causes a striking impairment of tissue homeostasis and functionality, particularly in the musculoskeletal system. Rejuvenation of the systemic and local milieu via interventions such as heterochronic parabiosis and exercise has been reported to improve musculoskeletal homeostasis in aged organisms. We have shown that Ginkgolide B (GB), a small molecule from Ginkgo biloba, improves bone homeostasis in aged mice by restoring local and systemic communication, implying a potential for maintaining skeletal muscle homeostasis and enhancing regeneration. In this study, we investigated the therapeutic efficacy of GB on skeletal muscle regeneration in aged mice.

methodsMuscle injury models were established by barium chloride induction into the hind limb of 20-month-old mice (aged mice) and into C2C12-derived myotubes. Therapeutic efficacy of daily administrated GB (12 mg/kg body weight) and osteocalcin (50 μg/kg body weight) on muscle regeneration was assessed by histochemical staining, gene expression, flow cytometry, ex vivo muscle function test and rotarod test. RNA sequencing was used to explore the mechanism of GB on muscle regeneration, with subsequent in vitro and in vivo experiments validating these findings.

resultsGB administration in aged mice improved muscle regeneration (muscle mass, P = 0.0374; myofiber number/field, P = 0.0001; centre nucleus, embryonic myosin heavy chain-positive myofiber area, P = 0.0144), facilitated the recovery of muscle contractile properties (tetanic force, P = 0.0002; twitch force, P = 0.0005) and exercise performance (rotarod performance, P = 0.002), and reduced muscular fibrosis (collagen deposition, P < 0.0001) and inflammation (macrophage infiltration, P = 0.03). GB reversed the aging-related decrease in the expression of osteocalcin (P < 0.0001), an osteoblast-specific hormone, to promote muscle regeneration. Exogenous osteocalcin supplementation was sufficient to improve muscle regeneration (muscle mass, P = 0.0029; myofiber number/field, P < 0.0001), functional recovery (tetanic force, P = 0.0059; twitch force, P = 0.07; rotarod performance, P < 0.0001) and fibrosis (collagen deposition, P = 0.0316) in aged mice, without an increased risk of heterotopic ossification.

conclusionsGB treatment restored the bone-to-muscle endocrine axis to reverse aging-related declines in muscle regeneration and thus represents an innovative and practicable approach to managing muscle injuries. Our results revealed the critical and novel role of osteocalcin-GPRC6A-mediated bone-to-muscle communication in muscle regeneration, which provides a promising therapeutic avenue in functional muscle regeneration.

Indexed as

Bone and BonesMuscle, SkeletalAnimalsGinkgolidesLactonesMiceMuscle Fibers, SkeletalOsteocalcinReceptors, G-Protein-Coupledginkgolide BGinkgolidesGPRC6A protein, mouseLactonesOsteocalcinReceptors, G-Protein-CoupledagingGinkgolide Bosteocalcinrejuvenationskeletal muscle regeneration

Identifiers

PMID37076950
PMCPMC10235878
OpenAlexW4366464151

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.