title: Evidence that the cells responsible for marrow fibrosis in a rat model for hyperparathyroidism are preosteoblasts.
abstract: We examined proliferation of cells associated with PTH-induced peritrabecular bone marrow fibrosis in rats as well as the fate of those cells after withdrawal of PTH. Time-course studies established that severe fibrosis was present 7 d after initiation of a continuous sc PTH infusion (40 microg/kg.d). To ascertain cell proliferation, rats were coinfused for 1 wk with PTH (treated) or vehicle (control) and [3H]thymidine (1.5 mCi/rat). Groups of control and treated rats were killed immediately (d 0) and 1 wk (d 7) later. Few osteoblasts (Obs) and osteocytes in treated and control groups were radiolabeled on d 0. Peritrabecular cells expressing a fibroblastic (Fb) phenotype and surrounded by an extracellular matrix were not present in controls on either d 0 or d 7. Multiple cell layers of Fbs lined most (70%) of the bone surface on d 0 in treated rats and nearly all (85%) of the Fbs were radiolabeled. Fbs had entirely disappeared from bone surfaces on d 7. Eighty-five percent of the Obs on and 73% of the osteocytes within the active remodeling sites were radiolabeled. Immunohistochemistry revealed that Fbs induced by PTH treatment produced osteocalcin, osteonectin, and core binding factor-alpha1. These data provide compelling evidence that Fbs recruited to bone surfaces in response to a continuous PTH infusion undergo extensive proliferation, express osteoblast-specific proteins, and produce an extracellular matrix that is similar to osteoid. After restoration of normal PTH levels, Fbs differentiated to Obs, providing further evidence that Fbs are preosteoblasts.
authors.affiliation: Department of Nutrition and Exercise Science, 108 Milam Hall, Oregon State University, Corvallis, Oregon 97331, USA.
authors.forename: Sutada
authors.initials: S
authors.lastname: Lotinun
authors.forename: Jean D
authors.initials: JD
authors.lastname: Sibonga
authors.forename: Russell T
authors.initials: RT
authors.lastname: Turner
mesh_terms: D000818:Animals; D001835:Body Weight; D050660:Core Binding Factors; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000473:pathology; D005260:Female; D006961:Hyperparathyroidism / Q000139:chemically induced / Q000473:pathology*; D009363:Neoplasm Proteins / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology*; D015675:Osteocalcin / Q000378:metabolism; D015676:Osteonectin / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood / Q000494:pharmacology; D055728:Primary Myelofibrosis / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D013936:Thymidine / Q000493:pharmacokinetics; D014157:Transcription Factors / Q000378:metabolism; D014316:Tritium
chemical_list: D050660:Core Binding Factors; D009363:Neoplasm Proteins; D015676:Osteonectin; D010281:Parathyroid Hormone; D014157:Transcription Factors; D014316:Tritium; D015675:Osteocalcin; D013936:Thymidine