LOCALIZATION OF PARATHYROID HORMONE-RELATED PROTEIN IN OSTEOCLASTS BYIN-SITU HYBRIDIZATION AND IMMUNOHISTOCHEMISTRY

Using immunohistology with two specific antisera raised against N-term inal parathyroid hormone-related protein (PTHrP) and in situ hybridiza tion (riboprobe to common coding exon), evidence is provided for the e xpression of PTHrP by mouse, rabbit, and human osteoclasts derived fro m several in vitro and in vivo sources, In cocultures of mouse bone ma rrow and calvarial cells treated with 1,25-dihydroxyvitamin D-3, the g enerated osteoclasts expressed both PTHrP messenger RNA (mRNA) and pro tein, In addition, PTHrP was detected in the majority of actively reso rbing osteoclasts in sections of newborn and adult mouse long bones, U sing an in vivo intramembranous bone formation model in rabbits, expre ssion of PTHrP mRNA and protein was demonstrated in osteoclasts at act ive bone resorption sites as well as in actively synthesizing osteobla sts and bone lining cells, Localization of PTHrP was also demonstrated in osteoclast-like cells of human giant cell tumors from bone, In som e of these tumors, a small proportion of the multinucleated cells expr essed tartrate resistant acid phosphatase (TRAP), but not PTHrP mRNA o r protein. Finally, both mRNA and protein for PTHrP were expressed in osteoclasts in sections of bone or joints from patients with Paget's d isease, rheumatoid arthritis, and osteoarthritis. These observations r aise the possibility that PTHrP might participate in osteoclast functi on. (C) 1998 by Elsevier Science Inc. All rights reserved.