title: Response to parathyroid hormone and 1,25-dihydroxyvitamin D3 of bone-derived cells isolated from normal children and children with abnormalities in skeletal development.
abstract: In order to evaluate the role of intrinsic defects in osteoblast function in the pathogenesis of diseases of skeletal development, we developed techniques which permit the evaluation of the metabolic properties of bone-derived cells in vitro. Cells from control children demonstrated a variety of properties classically attributed to osteoblasts (presence of alkaline phosphatase positive cells and synthesis of bone gla protein) and responded to PTH (cAMP production) and to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) ([3H]25-hydroxyvitamin D3 conversion into [3H]24,25-dihydroxyvitamin D3 and bone gla protein secretion). Using these techniques we evaluated the function of cultured bone cells from patients with three rare diseases of skeletal development. Cells from a patient with rickets resistant to 1,25(OH)2D3 were resistant to 1,25(OH)2D3 but responded normally to PTH. Cells from a patient with acroosteolysis with osteoporosis responded normally to PTH and 1,25(OH)2D3. Cells from a patient with hyperphosphatasia with osteoectasia responded normally to 1,25(OH)2D3 but did not respond to PTH. The results demonstrate that bone cell cultures can provide information about the role of osteoblast dysfunction in such diseases.
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D001848:Bone Diseases, Developmental / Q000378:metabolism*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D002648:Child; D002675:Child, Preschool; D000242:Cyclic AMP / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System; D005260:Female; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D015675:Osteocalcin; D010024:Osteoporosis / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D013250:Steroid Hydroxylases / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D002135:Calcium-Binding Proteins; D010281:Parathyroid Hormone; D015675:Osteocalcin; D003577:Cytochrome P-450 Enzyme System; D000242:Cyclic AMP; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D000469:Alkaline Phosphatase; D002117:Calcitriol