Interdependence of skeletal sclerosis and elevated circulating levels of 1,25-dihydroxyvitamin D in osteopetrotic (op and tl) rats.

摘要: Abstract Osteopetrosis describes a heterogeneous group of inherited, metabolic bone disorders characterized by reduced resorption which coexists with elevated circulating levels 1,25-dihydroxyvitamin D [1,25(OH) 2 D]. To determine whether or not skeletal sclerosis and high concentrations 1,25(OH) are interdependent, this study used two distinct, nonallelic osteopetrotic mutations in the rat, osteopetrosis ( op ) toothless tl ). The rat is mutation can be cured (mutant) induced (normal) following transfer normal mutant osteoclast progenitors, respectively. Although these procedures ineffective rats stock, infusions pharmacological doses macrophage colony-stimulating factor (CSF-1) stimulate eliminate most excess matrix mutants. This examined effects cure/ induction neonatal mutant/normal stock CSF-1 on (bone resorption) serum D] parameters as function time after treatment. Osteopetrotic mutants transplanted (cured) spleen cells demonstrated cellular changes phenotype within 2–3 days followed histologic radiographic evidence for increased that culminated appearance skeleton 4 weeks. markedly observed untreated fell significantly end first week were similar to those littermates at 3 Normal (induced) showed progressive increase paralleled significant increases D. Mutants infused period weeks reduction normalization levels. These data clearly demonstrate an interdependence between hypofunction rats.