Objective: 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is a key molecule to maintain calcium homeostasis and bone metabolism. It was recently reported that 1,25(OH)2D3 directly inhibited osteoclast differentiation in mouse bone marrow cells and human bone marrow-derived colony-forming unit granulocyte macrophage (CFU-GM) cells. However, the direct effects of 1,25(OH)2D3 and its affecting mechanisms on the osteoclast differentiation of human osteoclast precursors remain largely unknown. In this study, we examined the direct effects of 1,25(OH)2D3 on the osteoclastogenesis of human peripheral blood (PB) osteoclast precursors.
Methods: In vitro osteoclastogenesis assays were performed using osteoclast precursors from normal PB. The gene expressions were analyzed using real-time PCR. The cell surface proteins, including c-Fms and RANK, were measured by flow cytometry.
Results: 1,25(OH)2D3 strongly inhibited osteoclast differentiation and it suppressed the expression of RANK in the human PB osteoclast precursors. One mechanism of RANK inhibition by 1,25(OH)2D3 is down-regulation of the M-CSF receptor c-Fms, which is required for the expression of RANK. In contrast to the previous reports on mouse osteoclast precursors, 1,25(OH)2D3 did not affect the expression of c-Fos. Parallel to the inhibition of osteoclastogenesis, 1,25(OH)2D3 increased the expression and phosphorylation of CCAAT enhancer-binding protein β (C/EBPβ), which is a recently discovered inhibitor of osteoclastogenesis.
Conclusions: Our results show that 1,25(OH)2D3 inhibits human osteoclastogenesis by decreasing the RANK+ osteoclast precursors, and we suggest that 1,25(OH)2D3 may be a powerful therapeutic agent for treating inflammation-induced bone disease that shows excessive osteoclast activation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jbspin.2012.09.011 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Denatonium inhibits RANKL-induced osteoclast differentiation and rescues the osteoporotic phenotype by blocking p65 signaling pathway.
Mol Med
December 2024
Department of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Background: Bone remodeling is a critical process that maintains skeletal integrity, orchestrated by the balanced activities of osteoclasts, which resorb bone, and osteoblasts, which form bone. Osteoclastogenesis, the formation of osteoclasts, is primarily driven by NFATc1, a process activated through c-Fos and NF-κB signaling pathways in response to receptor activator of nuclear factor κB ligand (RANKL). Dysregulation of RANKL signaling is a key contributor to pathological bone loss, as seen in conditions such as osteoporosis.
View Article and Find Full Text PDFProtective effects of miR-24-2-5p in early stages of breast cancer bone metastasis.
Breast Cancer Res
December 2024
Research Unit UMR_S1033, LyOS, Faculty of Medicine Lyon-Est, INSERM, 7 Rue Guillaume Paradin, Lyon, 69372, France.
Background: Bone is the most frequent site of metastasis for breast cancer (BC). Metastatic BC cells interact with bone cells, including osteoclasts and osteoblasts, creating a cancer niche where they seed and proliferate. MicroRNAs (miRNAs) are regulators of breast-to-bone metastasis progression.
View Article and Find Full Text PDFRelationship between neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio and osteoporosis in postmenopausal type 2 diabetic patients: A retrospective study.
Medicine (Baltimore)
December 2024
School of Clinical Medicine, Shandong Second Medical University, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong Province, China.
Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) are newly discovered inflammatory markers in recent years. To explore the relationship between NLR, MLR, PLR, and bone mineral density (BMD), as well as osteoporosis (OP), in postmenopausal patients with type 2 diabetes mellitus (T2DM). 320 postmenopausal patients with T2DM who were admitted to the Department of Endocrinology and Metabolic Diseases of our hospital from January 2022 to January 2024 for treatment were included in this retrospective study.
View Article and Find Full Text PDFLysine specific demethylase 1 conditional myeloid cell knockout mice have decreased osteoclast differentiation due to increased IFN- gene expression.
JBMR Plus
January 2025
Division of Orthodontics, Department of Developmental and Surgical Sciences, University of Minnesota School of Dentistry, Minneapolis, MN 55455, United States.
Article Synopsis
- * The study found that removing the gene LSD1 in myeloid cells (which develop into osteoclasts) leads to increased bone mass and smaller osteoclasts in mice, indicating its role in bone health.
- * The research suggests that LSD1 influences osteoclast differentiation by affecting gene expression, specifically by interacting with other proteins that modify histones, ultimately impacting how osteoclasts function.
Deep phenotyping of T regulatory cells in psoriatic arthritis highlights targetable mechanisms of disease.
J Biol Chem
December 2024
Biosciences Institute, Newcastle University; NIHR, Biomedical Research Centre. Electronic address:
Regulatory T cells (Tregs) are immune regulatory T cells that are vital for controlling inflammation. The role of Tregs in inflammatory diseases namely Psoriatic Arthritis (PsA) is still poorly understood. The underlying reason being a lack of robust unbiased analysis to test the immune regulatory phenotype of human Tregs.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!