Calcified Tissue International

, Volume 37, Issue 3, pp 300–306 | Cite as

Evidence for two pathways for stimulation of collagenolysis in bone

  • Robert L. Jilka
  • James W. Hamilton
Laboratory Investigations


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 words

Collagenolysis Bone resorption Parathormone Calcitonin Interleukin-1 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Teitelbaum SL, Stewart CC, Kahn AJ (1979) Rodent peritoneal macrophages as bone resorbing cells. Calcif Tissue Int 27:255–261PubMedCrossRefGoogle Scholar
  2. 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. 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
  4. 4.
    Burleigh MC, Barrett AJ, Lazarus GS (1974) Cathespin B1, a lysosomal enzyme that degrades native collagen. Biochem J 137:387–398PubMedGoogle Scholar
  5. 5.
    Heersche JNM (1978) Mechanism of osteoclastic bone resorption: a new hypothesis. Calcif Tissue Res 26:81–84PubMedCrossRefGoogle Scholar
  6. 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
  7. 7.
    Brand JS, Raisz LG (1972) Effects of thyrocalcitonin and phosphate ion on the parathyroid hormone-stimulated resorption of bone. Endocrinology 90:479–487PubMedGoogle Scholar
  8. 8.
    Marks Jr SC (1977) Pathogenesis of osteopetrosis in the microphthalmic mouse: reduced bone resorption. Am J Anat 149:269–276PubMedCrossRefGoogle Scholar
  9. 9.
    Holtrop ME, Cox KA, Eilon G, Simmons HA, Raisz LG (1981) The ultrastructure of osteoclasts in the microphthalmic mouse. Metab Bone Dis Rel Res 3:123–129CrossRefGoogle Scholar
  10. 10.
    Jilka RL, Cohn DV (1983) A collagenolytic response to parathormone, 1,25-dihydroxycholecalciferol D3 and prostaglandin E2 in bone of osteopetrotic (mi/mi) mice. Endocrinology 122:945–950CrossRefGoogle Scholar
  11. 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. 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. 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. 14.
    Sakamoto M, Sakamoto S (1984) Immunocytochemical localization of collagenase in isolated mouse bone cells. Biomed Res 5:29–38Google Scholar
  15. 15.
    Francois-Gillet C, Delaisse JM, Eeckhout Y, Vaes G (1981) Immuoreactive collagenase and bone resorption. Biochem Biophys Acta 673:1–9PubMedGoogle Scholar
  16. 16.
    Lenaers-Claeys G, Vaes G (1979) Collagenase, procollagenase and bone resorption. Effects of heparin, parathyroid hormone and calcitonin. Biochem Biophys Acta 584:375–388PubMedGoogle Scholar
  17. 17.
    Hausmann E, Raisz LG, Miller WA (1970) Endotoxin: stimulation of bone resorption in tissue culture. Science 168:862–864PubMedCrossRefGoogle Scholar
  18. 18.
    Gowen M, Wood DD, Ihrie EJ, macGuire MKB, Russell RGG (1983) An interleukin-1-like factor stimulates bone resorption in vitro. Nature 306:378–380PubMedCrossRefGoogle Scholar
  19. 19.
    Waite LC, Volkert WA, Kenny AD (1970) Inhibition of bone resorption by acetazolamide in the rat. Endocrinology 87:1129–1139PubMedGoogle Scholar
  20. 20.
    Minkin C, Jennings JM (1972) Carbonic anhydrase and bone remodeling:O sulfonamide inhibition of bone resorption in organ culture. Science 176:1031–1033PubMedCrossRefGoogle Scholar
  21. 21.
    Anderson RE, Schraer H, Gay CV (1982) Ultrastructural and immunocytochemical localization of carbonic anhydrase in normal and calcitonin-treated chick osteoclasts. Anat Rec 204:9–20PubMedCrossRefGoogle Scholar
  22. 22.
    Delaisse JM, Eeckhout Y, Vaes G (1980) Inhibition of bone resorption in culture by inhibitors of thiol proteinases. Biochem J 192:365–368PubMedGoogle Scholar
  23. 23.
    Kent GN, Walker DG, Cohn DV (1979) Decreased response to calcitonin in osteopetrotic microphthalmic mouse bone. Nature 280:71–72PubMedCrossRefGoogle Scholar
  24. 24.
    Luben RA, Cohn DV (1976) Effects of parathormone and calcitonin on citrate and hydaluronate metabolism in cultured bone. Endocrinology 98:413–419PubMedGoogle Scholar
  25. 25.
    Chambers TJ, Revell PA, Fuller K, Athanasou NA (1984) Resorption of bone by isolated rabbit osteoclasts. J Cell Sci 66:383–399PubMedGoogle Scholar
  26. 26.
    Feldman RS, Kreiger NS, Tashjian Jr AH (1980) Effects of parathyroid hormone and calcitonin on osteoclast formation in vitro. Endocrinology 107:1137–1143PubMedGoogle Scholar
  27. 27.
    Kreiger NS, Feldman RS, Tashjian Jr AH (1982) Parathyroid hormone and calcitonin interactions in bone: irradiation-induced inhibition of escape in vitro. Calcif Tissue Int 34:197–203CrossRefGoogle Scholar
  28. 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
  29. 29.
    Vaes G (1968) On the mechanisms of bone resorption. The action of parathyroid hormone on the excretion and synthesis of lysosomal enzymes and ont he extracellular release of acid by bone cells. J Cell Biol 39:676–697PubMedCrossRefGoogle Scholar
  30. 30.
    Eeckhout Y, Vaes G (1977) Further studies on the activation of procollagenase, the latent precursor of bone collagenase. Biochem J 166:21–31PubMedGoogle Scholar
  31. 31.
    Raisz LG, Simmons HA, Gworek SC, Eilon G (1977) Studies on cogenital osteopetrosis in microphthalmic mice using organ cultures: impairment of bone resorption in response to physiologic stimulators. J Exp Med 145:857–865PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Robert L. Jilka
    • 1
    • 2
  • James W. Hamilton
    • 1
    • 2
  1. 1.Calcium Research LaboratoryVA Medical CenterKansas City
  2. 2.Department of BiochemistryUniversity of Kansas Medical CenterKansas CityUSA

Personalised recommendations