ArticleAmerican journal of physiology. Cell physiology2022
Calcium released by osteoclastic resorption stimulates autocrine/paracrine activities in local osteogenic cells to promote coupled bone formation.
Article in American journal of physiology. Cell physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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.
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.
Who cites it
11 citing papers in PubMed, 24 citations in OpenAlex.
- Orai1 is Required for Osteogenic Differentiation on Nanoparticulate Mineralized Collagen Glycosaminoglycan Materials.Macromolecular bioscience · 2025Article
- Osteoinductive low-dose 3D porous calcium phosphate graphene oxide-integrated matrices enhance osteogenesis and mechanical properties.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Efferocytosis and Bone Dynamics.Current osteoporosis reports · 2024Review
- Photothermal Antibacterial and Osteoinductive Polypyrrole@Cu Implants for Biological Tissue Replacement.Materials (Basel, Switzerland) · 2024Article
- Kalkitoxin attenuates calcification of vascular smooth muscle cells via RUNX-2 signaling pathways.Journal of veterinary science · 2023Article
- Examining Mechanisms for Voltage-Sensitive Calcium Channel-Mediated Secretion Events in Bone Cells.Calcified tissue international · 2023Review
- Bone mineralisation and glucose metabolism.Current opinion in endocrine and metabolic research · 2023Review
- The roles of bone remodeling in normal hematopoiesis and age-related hematological malignancies.Bone research · 2023Review
- Progress of Wnt Signaling Pathway in Osteoporosis.Biomolecules · 2023Review
- Targeting Tumor Microenvironment by Metal Peroxide Nanoparticles in Cancer Therapy.Bioinorganic chemistry and applications · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
A major cause of osteoporosis is impaired coupled bone formation. Mechanistically, both osteoclast-derived and bone-derived growth factors have been previously implicated. Here, we hypothesize that the release of bone calcium during osteoclastic bone resorption is essential for coupled bone formation. Osteoclastic resorption increases interstitial fluid calcium locally from the normal 1.8 mM up to 5 mM. MC3T3-E1 osteoprogenitor cells, cultured in a 3.6 mM calcium medium, demonstrated that calcium signaling stimulated osteogenic cell proliferation, differentiation, and migration. Calcium channel knockdown studies implicated calcium channels, Cav1.2, store-operated calcium entry (SOCE), and calcium-sensing receptor (CaSR) in regulating bone cell anabolic activities. MC3T3-E1 cells cultured in a 3.6 mM calcium medium expressed increased gene expression of Wnt signaling and growth factors platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and bone morphogenic protein-2 (BMP 2). Our coupling model of bone formation, the receptor activator of nuclear factor-κΒ ligand (RANKL)-treated mouse calvaria, confirmed the role of calcium signaling in coupled bone formation by exhibiting increased gene expression for osterix and osteocalcin. Critically, dual immunocytochemistry showed that RANKL treatment increased osterix-positive cells and increased fluorescence intensity of Cav1.2 and CaSR protein expression per osterix-positive cell. The above data established that calcium released by osteoclasts contributed to the regulation of coupled bone formation. CRISPR/Cas-9 knockout of Cav1.2 in osteoprogenitor cells cultured in basal calcium medium caused a >80% decrease in the expression of downstream osteogenic genes, emphasizing the large magnitude of the effect of calcium signaling. Thus, calcium signaling is a major regulator of coupled bone formation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.