Human growth hormone stimulates proteinase activities of rabbit bone cells via IGF-I.
Human growth hormone (hGH) and human insulin-like growth factor-I (hIGF-I) are known to have a marked influence on osteoclastic formation and bone resorption in an unfractionated rabbit bone cell model. This study investigated the effects of both of these factors on the induction of cysteine-proteinases and matrix metalloproteinase-2 (MMP-2) and MMP-9. After 4 days of rabbit bone cell culture, hGH and hIGF-I significantly modulated cathepsin, MMP-9 (latent form) and MMP-2 (active form) activities. Similar studies were performed in the presence of parathyroid hormone (hPTH). hPTH increased MMP-2 and MMP-9 activities whereas it had no effect on the production of cathepsins by bone cells. When neutralizing anti-hIGF-1 antiserum was added to the culture, the stimulatory effects of hGH were totally abolished, indicating that hGH-modulated cathepsin and metalloproteinase activities were partly mediated by local hIGF-I secretion. Cysteine-proteinase activities released by purified osteoclasts were very low and were not modulated by hGH and h-IGF-I. However, hIGF-I but not hGH increased MMP-2 and MMP-9 activities released by purified osteoclasts. It may be concluded that hGH markedly stimulates the expression of proteinases in total rabbit bone cells via local hIGF-I production by stromal cells. Cysteine-proteinase activities are mainly produced by non-osteoclastic cells, while MMP-2 and MMP-9 modulated by hIGF-I are mainly expressed by osteoclastic cells.
Anne-Valérie
R
R
Faculté de Chirurgie Dentaire, 1 place A. Ricordeau, Nantes cedex 1, 44042, France.
Christelle
D
D
Yannick
F
F
Norbert
P
P
Marc
P
P
Dominique
H
H
D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D002403:Cathepsins / Q000378:metabolism; D002478:Cells, Cultured; D010450:Endopeptidases / Q000378:metabolism*; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology
D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D002403:Cathepsins; D010450:Endopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9