ArticlePeerJ2021
Undercarboxylated osteocalcin inhibits the early differentiation of osteoclast mediated by Gprc6a.
Article in PeerJ, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- ucOCN Promotes Testosterone Synthesis via the PKA-MAPK/ERK-CREB Signaling Pathway in Porcine Leydig Cells.Cells · 2025Article
- Parathyroid Hormone as a Modulator of Skeletal Muscle: Insights into Bone-Muscle and Nerve-Muscle Interactions.International journal of molecular sciences · 2025Review
- Osteocalcin and GPR158: linking bone and brain function.Frontiers in cell and developmental biology · 2025Review
- The function of GPCRs in different bone cells.International journal of biological sciences · 2025Review
- Association between bone mineral density T-score and respiratory sarcopenia in older adults.Frontiers in medicine · 2025Article
- Study on the correlation between abnormal bone metabolism and cognitive impairment in type 2 diabetes mellitus.Frontiers in medicine · 2025Article
- The Role of Bone-Derived Osteocalcin in Testicular Steroidogenesis: Contributing Factor to Male Fertility.Diseases (Basel, Switzerland) · 2024Review
- Bone-muscle crosstalk under physiological and pathological conditions.Cellular and molecular life sciences : CMLS · 2024Review
- Hyperglycemia from Diabetes Potentiates Uncarboxylated Osteocalcin-Stimulated Insulin Secretion in Rat INS-1 Pancreatic β-Cells.Nutrients · 2024Article
- Comparative Analysis of Myokines and Bone Metabolism Markers in Prepubertal Vegetarian and Omnivorous Children.Nutrients · 2024Article
- Review
- Mechanism and physical activities in bone-skeletal muscle crosstalk.Frontiers in endocrinology · 2023Review
- Osteocalcin and the physiology of danger.FEBS letters · 2022Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteocalcin (OCN) was the most abundant noncollagen protein and considered as an endocrine factor. However, the functions of Undercarboxylated osteocalcin (ucOCN) on osteoclast and bone resorption are not well understood. In the present study, preosteoclast RAW264.7 cells and bone marrow mononuclear cells (BMMs) were treated with ucOCN purified from prokaryotic bacteria. Our results showed that ucOCN attenuated the proliferation of RAW264.7 cells with a concentration dependant manner by MTS assay. Scrape wounding assay revealed the decreased motility of RAW264.7 cells after ucOCN treatment. RT-qPCR results manifested the inhibitory effects of ucOCN on the expression of osteoclastic marker genes in RAW264.7 cells during inducing differentiation of RANKL. It was also observed that ucOCN inhibited the formation of multinucleated cells from RAW264.7 cells and BMMs detected by TRAP staining. The number and area of bone resorb pits were also decreased after treatment with ucOCN during their osteoclast induction by toluidine blue staining. The formation and integrity of the osteoclast actin ring were impaired by ucOCN by immunofluorescent staining. Time dependant treatment of ucOCN during osteoclastic induction demonstrated the inhibitory effects mainly occurred at the early stage of osteoclastogenesis. Signaling analysis of luciferase activity of the CRE or SRE reporter and ERK1/2 phosphorylation showed the selective inhibitor or siRNA of Gprc6a (a presumptive ucOCN receptor) could attenuate the promotion of ucOCN on CRE-luciferase activity. Taken together, we provided the first evidence that ucOCN had negative effects on the early differentiation and bone resorption of osteoclasts via Gprc6a.
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