Clinical characteristics influence in vitro action of 1,25-dihydroxyvitamin D3 in human marrow stromal cells

Shuanhu Zhou, Julie Glowacki, Sung Won Kim, Jochen Hahne, Shuo Geng, Stefan M. Mueller, Longxiang Shen, Ilan Bleiberg, Meryl S. LeBoff

Research output: Contribution to journalArticlepeer-review

Abstract

Vitamin D is important for bone health, with low vitamin D levels being associated with skeletal fragility and fractures. Among its other biological activities, 1,25-dihydroxyvitamin D (1,25(OH)2D), stimulates the in vitro differentiation of human marrow stromal cells (hMSCs) to osteoblasts, which can be monitored by increases in alkaline phosphatase enzyme activity or osteocalcin gene expression. In this study, we tested the hypotheses that age and clinical attributes of subjects influence in vitro responsiveness of hMSCs to 1,25(OH)2D3. In a cohort of subjects whose hMSCs were isolated from bone marrow discarded during hip replacement surgery for osteoarthritis, there were significant inverse correlations with age for bone mineral density, renal function, body mass index, fat mass index, and lean mass index (n = 36-53). There were significant correlations with serum 25(OH)D for serum parathyroid hormone (PTH), body mass index, fat mass index, and lean mass index (n = 47-50). In vivo-in vitro correlation analyses indicated that there were significantly greater in vitro effects of 1,25(OH)2D3 to stimulate osteoblast differentiation in hMSCs obtained from subjects who were younger than 65 years of age, or who had serum 25(OH)D ≤ 20ng/mL, elevated serum PTH, or better renal function, assessed by estimated glomerular filtration rate. The greater in vitro stimulation of osteoblast differentiation by 1,25(OH)2D3 in hMSCs from vitamin D-deficient subjects suggests that vitamin D replenishment may lead to more vigorous bone formation in subjects at risk.

Original languageEnglish
Pages (from-to)1992-2000
Number of pages9
JournalJournal of Bone and Mineral Research
Volume27
Issue number9
DOIs
StatePublished - Sep 2012

Keywords

  • AGE
  • MARROW STROMAL CELLS
  • OSTEOBLAST DIFFERENTIATION
  • VITAMIN D
  • eGFR

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