TY - JOUR
T1 - Bone‐resorbing agents promote and interferon‐γ inhibits bone cell collagenase production
AU - Shen, Victor
AU - Kohler, Gail
AU - Jeffrey, John J.
AU - Peck, William A.
PY - 1988/12
Y1 - 1988/12
N2 - Parathyroid hormone, prostaglandin E2, 1α,25‐dihydroxyvitamin D3, interleukin‐1, tumor necrosis factor α, and epidermal growth factor, all known stimulators of bone resorption, markedly enhanced collagenase secretion by rat fetus osteoblastlike cells in primary culture as judged by enzyme‐linked immunosorbent assay. Untreated cells contained no immunostainable or extractable collagenase. Collagenase was detected in the treated cells and media only after 1–3 h of treatment, and there was no increment in collagenase activity when cells were treated in the presence of actinomycin D or cycloheximide. Cells secreted collagenase in a latent form and also elaborated collagenase inhibitor; chromatographic separation of collagenase from collagenase inhibitor and subsequent activation of the collagenase with trypsin yielded the active species in stimulated but not in unstimulated cells. The ability of individual prostanoids, among seven tested, to promote collagenase production correlated positively with their reported capacity to promote bone resorption. Interferon‐γ (IFN‐γ), a known resorption inhibitor, blocked the increment in collagenase production caused by all agents tested. These results indicate a close linkage between stimulation of bone resorption and collagenase production by osteoblastlike cells. Various resorption stimulators, including some not previously tested for effects on collagenase, augment the de novo synthesis and secretion of collagenase and act by an IFN‐γ‐inhibitable mechanism.
AB - Parathyroid hormone, prostaglandin E2, 1α,25‐dihydroxyvitamin D3, interleukin‐1, tumor necrosis factor α, and epidermal growth factor, all known stimulators of bone resorption, markedly enhanced collagenase secretion by rat fetus osteoblastlike cells in primary culture as judged by enzyme‐linked immunosorbent assay. Untreated cells contained no immunostainable or extractable collagenase. Collagenase was detected in the treated cells and media only after 1–3 h of treatment, and there was no increment in collagenase activity when cells were treated in the presence of actinomycin D or cycloheximide. Cells secreted collagenase in a latent form and also elaborated collagenase inhibitor; chromatographic separation of collagenase from collagenase inhibitor and subsequent activation of the collagenase with trypsin yielded the active species in stimulated but not in unstimulated cells. The ability of individual prostanoids, among seven tested, to promote collagenase production correlated positively with their reported capacity to promote bone resorption. Interferon‐γ (IFN‐γ), a known resorption inhibitor, blocked the increment in collagenase production caused by all agents tested. These results indicate a close linkage between stimulation of bone resorption and collagenase production by osteoblastlike cells. Various resorption stimulators, including some not previously tested for effects on collagenase, augment the de novo synthesis and secretion of collagenase and act by an IFN‐γ‐inhibitable mechanism.
UR - http://www.scopus.com/inward/record.url?scp=0024212337&partnerID=8YFLogxK
U2 - 10.1002/jbmr.5650030611
DO - 10.1002/jbmr.5650030611
M3 - Article
C2 - 2855191
AN - SCOPUS:0024212337
SN - 0884-0431
VL - 3
SP - 657
EP - 666
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 6
ER -