Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells.
Previous studies demonstrated that intermittent treatment with PTH increases osteoblast number and bone formation in growing and adult rats. The cellular mechanism for this increase in osteoblast number was investigated in 16-month-old female rats. Continuous [3H]thymidine infusion over a 1-week intermittent PTH [human PTH-(1-34)] treatment period was performed to determine the percentage of newly formed osteoblasts that originate from progenitor cells. To verify increases in bone formation, we performed histomorphometry and Northern blot analysis of selected bone matrix proteins. PTH treatment resulted in dramatic increases in fluorochrome-labeled perimeter (727%), osteoid perimeter (735%), osteoblast number (626%), and steady state mRNA levels of osteocalcin (946%) and type 1 collagen (> 1000%). Autoradiographic analysis of metaphyseal sections revealed no difference in the percentage of [3H]thymidine-labeled osteoblasts between PTH- and vehicle-treated groups (4.3 +/- 1.3% vs. 5.7 +/- 2.7%, respectively). Similar changes were observed in PTH-treated ovariectomized rats. As the PTH-induced increase in osteoblast number did not require proliferation of progenitor cells we carried out an additional experiment in adult ovariectomized rats to determine the onset of PTH action. Incorporation of [3H]proline in the distal femoral epiphysis of PTH-treated adult ovariectomized rats was increased within 24 h. We conclude that the rapid PTH-induced rise in bone formation did not require cell proliferation and was most likely due to activation of preexisting bone lining cells to osteoblasts.
Dobnig
H
H
Department of Orthopedics, Mayo Clinic, Rochester, Minnesota 55905, USA.
Turner
R T
RT
D000818:Animals; D001345:Autoradiography; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D010012:Osteogenesis / Q000187:drug effects*; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000008:administration & dosage* / Q000494:pharmacology*; D011392:Proline / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000378:metabolism
D010281:Parathyroid Hormone; D011392:Proline; D013936:Thymidine