OSTEOBLASTS AND OSTEOCLASTS IN ADULT HUMAN OSTEOPHYTE TISSUE EXPRESS THE MESSENGER-RNAS FOR INSULIN-LIKE GROWTH-FACTOR-I AND GROWTH-FACTOR-II AND THE TYPE-1 IGF RECEPTOR

Insulin-like growth factors (IGFs) are among the most abundant growth factors present in bone. In vitro, bone-derived cells both produce and respond to IGFs I and II, suggesting that these growth factors play a n autocrine role in the regulation of bone turnover. In vivo, however, particularly in adult bone, their sites of expression have not been w ell documented, We have used, therefore, the technique of in situ hybr idization to study the expression of the mRNAs for IGFs I and II and t he type 1 IGF receptor in adult human osteophyte tissue. Throughout th e developing osteophyte there was a strong association between osteoge nesis and the expression of all three mRNA transcripts. The highest le vels of expression were observed in active osteoblasts. Hybridization signals were weak or absent in flat cells lining quiescent surfaces an d in cells of the bone marrow, including those that expressed alkaline phosphatase activity. Osteocytes and cells of the periosteum were neg ative. At sites of endochondral bone formation newly differentiated an d hypertrophic chondrocytes expressed the mRNAs for IGFs and IGF recep tor whereas cells of the perichondrium were negative. A striking findi ng of this investigation was that osteoclasts at sites of bone and cal cified cartilage resorption expressed high levels of all three mRNA tr anscripts. These results support the hypothesis that locally produced IGFs are important regulators of bone formation. The differential expr ession of all three transcripts among cells of the osteoblast lineage suggests that IGFs may be involved in the maintenance of the mature os teoblast phenotype rather than in inducing the differentiation of marr ow precursors or controlling the osteoblast-osteocyte transition. The demonstration that osteoclasts express all three mRNA transcripts sugg ests that IGFs may additionally participate in the autocrine and/or pa racrine regulation of bone resorption.