title: Clinical characteristics influence in vitro action of 1,25-dihydroxyvitamin D(3)  in human marrow stromal cells.
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)(2) D), 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)(2) D(3) . 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)(2) D(3) to stimulate osteoblast differentiation in hMSCs obtained from subjects who were younger than 65 years of age, or who had serum 25(OH)D ≤ 20 ng/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)(2) D(3) in hMSCs from vitamin D-deficient subjects suggests that vitamin D replenishment may lead to more vigorous bone formation in subjects at risk.
authors.affiliation: Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Shuanhu
authors.initials: S
authors.lastname: Zhou
authors.forename: Julie
authors.initials: J
authors.lastname: Glowacki
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Jochen
authors.initials: J
authors.lastname: Hahne
authors.forename: Shuo
authors.initials: S
authors.lastname: Geng
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Mueller
authors.forename: Longxiang
authors.initials: L
authors.lastname: Shen
authors.forename: Ilan
authors.initials: I
authors.lastname: Bleiberg
authors.forename: Meryl S
authors.initials: MS
authors.lastname: LeBoff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D002113:Calcification, Physiologic / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D008875:Middle Aged; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology
chemical_list: D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D000469:Alkaline Phosphatase