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 examinedin 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.
Key wordsCollagenolysis Bone resorption Parathormone Calcitonin Interleukin-1
Unable to display preview. Download preview PDF.
- 2.Ibbotson KJ, Roodman GD, Mundy GR (1983) Demonstration of authentic osteoclasts (OCL) in long-term marrow cell cultures. Calcif Tissue Int 35:643Google Scholar
- 3.Howard GA, Liu CC (1984) Osteoclasts sufficient for biochemical studies. In: Cohn DV, Fujita T, Potts Jr JT, Talmage RV (eds) Endocrine control of bone and calcium emtabolism. Exerpta Medica, Amsterdam, p 422.Google Scholar
- 6.Heersche JNM (1969) Resorption of bone collagen under the influence of parathyroid hormone and thyrocalcitonin. Proc Kon Med Akad Wet Ser C 71:80–84Google Scholar
- 11.Sakamoto S, Sakamoto M (1984) Isolation and characterization of collagenase synthesized by mouse bone cells in culture. Biomed Res 5:39–46Google Scholar
- 12.Jilka RL, Hamilton JW (1984) Involvement of nonosteoclastic cells in hormone regulated collagtenolysis bone. In: Cohn DV, Fujita T, Potts Jr JT, Talmage RV (eds) Endocrine control of bone and calcium metabolism. Excerpta Medica, Amsterdam, p 136–139Google Scholar
- 13.Braidman IP, Virani N, Anderson DC (1984) Properties and hormonal responses of rat bone cell collagenase. In: Cohn DV, Fujita T, Potts Jr JT, Talmage RV (eds) Endocrine control of bone and calcium metabolism. Excerpta Medica, Amsterdam, p 131–135Google Scholar
- 14.Sakamoto M, Sakamoto S (1984) Immunocytochemical localization of collagenase in isolated mouse bone cells. Biomed Res 5:29–38Google Scholar
- 28.Wener JA, Gorton SJ, Raisz LG (1972) Escape from inhibition of resorption in cultures of fetal bone treated with calcitonin and parathyroid hormone. Endocrinol 90:752–759Google Scholar