Evidence for two pathways for stimulation of collagenolysis in bone.
The effect of parathormone (PTH), lipopolysaccharide (LPS), or interleukin-1 (IL-1) on calcium release and collagen degradation in bone was examined in vitro using labeled neonatal calvaria of normal mice and also of osteopetrotic microphthalmic (mi/mi) mice that have defective osteoclasts. All three agents stimulated calcium release from normal bone but not from mi/mi bone. PTH stimulated the degradation of both noncalcified and calcified collagen in normal bone as well as the degradation of noncalcified collagen in mi/mi bone. However, LPS and IL-1 only stimulated the degradation of calcified collagen in normal bone. One-half maximal stimulation of noncalcified collagen degradation in normal or mi/mi bone was achieved by about 3 nM PTH compared with about 1 nM PTH for that of calcium release from normal bone. While calcitonin (CT) and leupeptin inhibited calcium release and thereby the degradation of calcified collagen, neither agent inhibited PTH-stimulated noncalcified collagen degradation in normal or mi/mi bone. The data indicate the existence of two pathways that lead to collagen degradation in bone. One is intimately connected with the resorptive process stimulated by a variety of agents, and is probably mediated by osteoclasts. A second mechanism is sensitive only to PTH and appears to be associated with nonosteoclastic cells since it can operate under conditions in which osteoclasts are thought to be inactive or are inhibited.
D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism*; D002116:Calcitonin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002356:Cartilage / Q000378:metabolism*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D010010:Osteoclasts / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology; D011392:Proline / Q000378:metabolism
D007375:Interleukin-1; D007976:Leupeptins; D008070:Lipopolysaccharides; D010281:Parathyroid Hormone; D002116:Calcitonin; D011392:Proline; C032854:leupeptin; D000086:Acetazolamide; D002118:Calcium