Vitamin D metabolism and action in human marrow stromal cells: effects of chronic kidney disease
Abstract
Human marrow stromal cells (hMSCs) are targets of 1α,25-dihydroxyvitamin D [1α,25(OH)2D3] action to promote their differentiation to osteoblasts, but they also participate in vitamin D metabolism by converting 25-dihydroxyvitamin D3 [25(OH)D3] to 1α,25(OH)2D3 by 1α-hydroxylase (CYP27B1). Chronic kidney disease (CKD) is associated with impaired renal biosynthesis of 1α,25(OH)2D, low bone mass, and increased fracture risk. We tested whether CKD influences hMSCs' responses to vitamin D3 metabolites. The hMSCs were obtained from tissues discarded during arthroplasty for hip osteoarthrosis, including a subject who had been undergoing hemodialysis for 2+ years. There was a significant positive correlation between in vitro stimulation of osteoblastogenesis (alkaline phosphatase activity) by 1α,25(OH)2D3 and subjects' estimated glomerular filtration rate (eGFR, r=0.47, p=0.015, n=26, 56-83 years of age). Osteoblastogenesis was stimulated in hMSCs from both the hemodialysis and control subjects by 1α,25(OH)2D3 (10μM), 25(OH)D3 (100μM), or D3 (1000μM). Thus, vitamin D metabolism may play an autocrine/paracrine role in osteoblast differentiation of hMSCs. These findings suggest that in CKD patients 25(OH)D-sufficiency may play an important role in skeletal health; osteoblastic bone formation in CKD patients may not be optimal unless there is sufficient serum 25(OH)D substrate for the MSCs to synthesize and respond to local 1α,25(OH)2D. This article is part of a Special Issue entitled…
Read the paper
Related studies
- Effectiveness of Bisphosphonates and Denosumab on Risk of Vertebral Fractures in Prostate Cancer Patients Under Androgen Deprivation Therapies: A Real-World Prospective Study
- Osteoporosis-related fractures after spinal cord injury: a retrospective study from Brazil
- Serum 25-hydroxyvitamin D, parathyroid hormone, and mortality in older men
- Lack of Association between Vitamin D Insufficiency and Cardiovascular or Fracture Risk: A UK Biobank Study
- Muscle strength and body composition are clinical indicators of osteoporosis
- Incidence of bone protection and associated fragility injuries in patients with proximal femur fractures
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.