Parathyroid hormone (1-34) regulates integrin expression in vivo in rat osteoblasts.
Intermittent administration of parathyroid hormone (PTH) activates new sites of bone formation by stimulating osteoblast differentiation and function resulting in an increase in bone mass. Because integrins have been shown to play a crucial role in osteoblast differentiation and bone formation, in the present study, we evaluated whether human PTH (1-34) upon administration to rats, influenced integrin expression in osteoblastic cells isolated from the metaphysis and the diaphysis of rat long bones. Initial immunohistochemical evaluation of bone sections demonstrated that the osteoblasts expressed at least alphav, alpha2, alpha3, and alpha5beta1 integrins. Immunocolocalization studies for integrins and vinculin established that alphav, alpha2, and alpha5beta1, but not alpha3 integrins were present in the focal adhesion sites of osteoblasts attached to FN coated surfaces. Osteoprogenitor cells isolated from metaphyseal (but not diaphyseal) marrow of rats injected with intermittent PTH (1-34) exhibited greater alphav and reduced alpha2 levels, with no apparent changes in alpha3, and alpha5beta1 integrin levels, as assessed by immunohistochemistry, Northern, and Western blot analyses. However, these changes were not observed on the same cells treated with PTH in vitro. These observations suggest that integrin modulation by PTH is likely to be indirect and that selective phenotypic expression of integrin subtypes is part of the cascade of events that lead to PTH (1-34) mediated osteoblast differentiation.
Kaiser
E
E
Gene Regulation, Bone, and Inflammation Research, DC0403, Lilly Research Laboratories, Eli Lilly and Company, Corporate Center, Indianapolis, IN 46285, USA.
Sato
M
M
Onyia
J E
JE
Chandrasekhar
S
S
D000818:Animals; D015153:Blotting, Western; D001842:Bone and Bones / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D004357:Drug Synergism; D005260:Female; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D016023:Integrins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000008:administration & dosage* / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured
D005353:Fibronectins; D016023:Integrins; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D012333:RNA, Messenger