ArticleInternational journal of biological sciences2013
1,25-Dihydroxyvitamin D3 activates MMP13 gene expression in chondrocytes through p38 MARK pathway.
Article in International journal of biological sciences, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 23 citations in OpenAlex.
- Computational design of MMP-13 inhibitors using a combined approach of machine learning, docking, and molecular dynamics.Molecular diversity · 2026Article
- Mechanisms Underlying the Stimulation of DUSP10/MKP5 Expression in Chondrocytes by High Molecular Weight Hyaluronic Acid.Biomedicines · 2025Article
- Relationship between DXA measured systemic bone mineral density and subchondral bone cysts in postmenopausal female patients with knee osteoarthritis: a cross-sectional study : Osteoarthritis cysts and bone mineral density.BMC musculoskeletal disorders · 2024Article
- Older Korean men with inadequate vitamin D status have lower odds of radiologic osteoarthritis.Scientific reports · 2022Article
- Vitamin D in the Prevention and Treatment of Osteoarthritis: From Clinical Interventions to Cellular Evidence.Nutrients · 2019Review
- Hormonal Regulation of Osteocyte Perilacunar and Canalicular Remodeling in the Hyp Mouse Model of X-Linked Hypophosphatemia.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2018Article
- Glucagon-like peptide-1 receptor regulates endoplasmic reticulum stress-induced apoptosis and the associated inflammatory response in chondrocytes and the progression of osteoarthritis in rat.Cell death & disease · 2018Article
- Protective effects of PI3K/Akt signal pathway induced cell autophagy in rat knee joint cartilage injury.American journal of translational research · 2018Article
- Co-expression of 1α-hydroxylase and vitamin D receptor in human articular chondrocytes.BMC musculoskeletal disorders · 2017Article
- 1,25(OH)2D3 Protects Liver Fibrosis Through Decreasing the Generation of TH17 Cells.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- 24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats.PloS one · 2016Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoarthritis (OA) is the most prevalent degenerative joint disease. The highly regulated balance of matrix synthesis and degradation is disrupted in OA, leading to progressive breakdown of articular cartilage. The molecular events and pathways involved in chondrocyte disfunction of cartilage in OA are not fully understood. It is known that 1,25-dihydroxyvitamin D₃(1,25-(OH)2D3) is synthesized by macrophages derived from synovial fluid of patients with inflammatory arthritis. Vitmain D receptor is expressed in chondrocytes within osteoarthritic cartilage, suggesting a contributory role of 1,25-(OH)2D3 in the aberrant behavior of chondrocytes in OA. However, the physiological function of 1,25-(OH)2D3 on chondrocytes in OA remains obscure. Effect of 1,25-(OH)2D3 on gene expression in chondrocytes was investigated in this study. We found that 1,25-(OH)2D3 activated MMP13 expression in a dose-dependent and time-dependent manner, a major enzyme that targets cartilage for degradation. Interestingly, a specific mitogen-activated protein kinase p38 inhibitor SB203580, but not JNK kinase inhibitor SP600125, abrogated 1,25-(OH)2D3 activation of MMP13 expression. 1,25-(OH)2D3-induced increase in MMP13 protein level was in parallel with the phosphorylation of p38 in chondrocytes. To further address the effect of 1,25-(OH)2D3 on MMP13 expression, transfection assays were used to show that 1,25-(OH)2D3 activated the MMP13 promoter reporter expression. MMP13 is known to target type II collagen and aggrecan for degradation, two major components of cartilage matrix. We observed that the treatment of 1,25-(OH)2D3 in chondrocytes results in downregulation of both type II collagen and aggrecan while MMP13 was upregulated. Taken together, we provide the first evidence to demonstrate that 1,25-(OH)2D3 activates MMP13 expression through p38 pathway in chondrocytes. Since MMP13 plays a major role in cartilage degradation in OA, we speculate that the ability of 1,25-(OH)2D3 to potentiate MMP13 expression might facilitate cartilage erosion at the site of inflammatory arthritis.
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