Evidence that the cells responsible for marrow fibrosis in a rat model for hyperparathyroidism are preosteoblasts.
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.
Lotinun
Sutada
S
Department of Nutrition and Exercise Science, 108 Milam Hall, Oregon State University, Corvallis, Oregon 97331, USA.
Sibonga
Jean D
JD
Turner
Russell T
RT
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
D050660:Core Binding Factors; D009363:Neoplasm Proteins; D015676:Osteonectin; D010281:Parathyroid Hormone; D014157:Transcription Factors; D014316:Tritium; D015675:Osteocalcin; D013936:Thymidine