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. 1998 Apr 15;101(8):1596–1603. doi: 10.1172/JCI867

Abnormal cancellous bone collagen metabolism in osteoarthritis.

J P Mansell 1, A J Bailey 1
PMCID: PMC508740  PMID: 9541489

Abstract

Biochemical investigations into the pathogenesis of osteoarthritis have, for the last two decades, concentrated on the mechanisms involved in the destruction of the articular cartilage. Although bone changes are known to occur, the biochemistry of the collagenous matrix within osteoarthritic bone has received scant attention. We report that bone collagen metabolism is increased within osteoarthritic femoral heads, with the greatest changes occurring within the subchondral zone. Collagen synthesis and its potential to mineralize were determined by the carboxy-terminal propeptide content and alkaline phosphatase activity, respectively. These data supported elevated new matrix formation. Our finding of a three- to fourfold increase in TGF-beta in osteoarthritic bone indicates that this might represent a stimulus for the increased collagen synthesis observed. Of additional significance is the hypomineralization of deposited collagen in the subchondral zone of osteoarthritic femoral heads, supporting a greater proportion of osteoid in the diseased tissue. The cross-linking of collagen was similar to that observed for controls. In addition, the degradative potential of osteoarthritic bone was considerably higher as demonstrated by increased matrix metalloproteinase 2 activity, and again the greater activity was associated with the subchondral bone tissue. The polarization exhibited in the metabolism of bone collagen from osteoarthritic hips might exacerbate the processes involved in joint deterioration by altering joint morphology. This in turn may alter the distribution of mechanical forces to the various tissues, to which bone is a sensitive responder. Bone collagen metabolism is clearly an important factor in the pathogenesis of osteoarthritis and certainly warrants further biochemical study.

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Selected References

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  1. Aimes R. T., Quigley J. P. Matrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4-length fragments. J Biol Chem. 1995 Mar 17;270(11):5872–5876. doi: 10.1074/jbc.270.11.5872. [DOI] [PubMed] [Google Scholar]
  2. Bailey A. J., Mansell J. P. Do subchondral bone changes exacerbate or precede articular cartilage destruction in osteoarthritis of the elderly? Gerontology. 1997;43(5):296–304. doi: 10.1159/000213866. [DOI] [PubMed] [Google Scholar]
  3. Bannister D. W., Burns A. B. Adaptation of the Bergman and Loxley technique for hydroxyproline determination to the autoanalyzer and its use in determining plasma hydroxyproline in the domestic fowl. Analyst. 1970 Jun;95(131):596–600. doi: 10.1039/an9709500596. [DOI] [PubMed] [Google Scholar]
  4. Batra H. C., Charnley J. Existence and incidence of osteoid in osteoarthritis femoral heads. A preliminary report. J Bone Joint Surg Br. 1969 May;51(2):366–371. [PubMed] [Google Scholar]
  5. Bell N. H., Gordon L., Stevens J., Shary J. R. Demonstration that bone mineral density of the lumbar spine, trochanter, and femoral neck is higher in black than in white young men. Calcif Tissue Int. 1995 Jan;56(1):11–13. doi: 10.1007/BF00298737. [DOI] [PubMed] [Google Scholar]
  6. Beresford J. N., Bennett J. H., Devlin C., Leboy P. S., Owen M. E. Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures. J Cell Sci. 1992 Jun;102(Pt 2):341–351. doi: 10.1242/jcs.102.2.341. [DOI] [PubMed] [Google Scholar]
  7. Bullen E. C., Longaker M. T., Updike D. L., Benton R., Ladin D., Hou Z., Howard E. W. Tissue inhibitor of metalloproteinases-1 is decreased and activated gelatinases are increased in chronic wounds. J Invest Dermatol. 1995 Feb;104(2):236–240. doi: 10.1111/1523-1747.ep12612786. [DOI] [PubMed] [Google Scholar]
  8. Büttner F. H., Chubinskaya S., Margerie D., Huch K., Flechtenmacher J., Cole A. A., Kuettner K. E., Bartnik E. Expression of membrane type 1 matrix metalloproteinase in human articular cartilage. Arthritis Rheum. 1997 Apr;40(4):704–709. doi: 10.1002/art.1780400415. [DOI] [PubMed] [Google Scholar]
  9. Delaissé J. M., Eeckhout Y., Neff L., François-Gillet C., Henriet P., Su Y., Vaes G., Baron R. (Pro)collagenase (matrix metalloproteinase-1) is present in rodent osteoclasts and in the underlying bone-resorbing compartment. J Cell Sci. 1993 Dec;106(Pt 4):1071–1082. doi: 10.1242/jcs.106.4.1071. [DOI] [PubMed] [Google Scholar]
  10. Dequeker J., Johnell O. Osteoarthritis protects against femoral neck fracture: the MEDOS study experience. Bone. 1993;14 (Suppl 1):S51–S56. doi: 10.1016/8756-3282(93)90350-j. [DOI] [PubMed] [Google Scholar]
  11. Dequeker J., Mohan S., Finkelman R. D., Aerssens J., Baylink D. J. Generalized osteoarthritis associated with increased insulin-like growth factor types I and II and transforming growth factor beta in cortical bone from the iliac crest. Possible mechanism of increased bone density and protection against osteoporosis. Arthritis Rheum. 1993 Dec;36(12):1702–1708. doi: 10.1002/art.1780361209. [DOI] [PubMed] [Google Scholar]
  12. Dequeker J., Mokassa L., Aerssens J. Bone density and osteoarthritis. J Rheumatol Suppl. 1995 Feb;43:98–100. [PubMed] [Google Scholar]
  13. Dieppe P., Cushnaghan J., Young P., Kirwan J. Prediction of the progression of joint space narrowing in osteoarthritis of the knee by bone scintigraphy. Ann Rheum Dis. 1993 Aug;52(8):557–563. doi: 10.1136/ard.52.8.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hillam R. A., Skerry T. M. Inhibition of bone resorption and stimulation of formation by mechanical loading of the modeling rat ulna in vivo. J Bone Miner Res. 1995 May;10(5):683–689. doi: 10.1002/jbmr.5650100503. [DOI] [PubMed] [Google Scholar]
  15. Jeffery A. K. Osteogenesis in the osteoarthritic femoral head. A study using radioactive 32 P and tetracycline bone markers. J Bone Joint Surg Br. 1973 May;55(2):262–272. [PubMed] [Google Scholar]
  16. Jones G., Nguyen T., Sambrook P. N., Lord S. R., Kelly P. J., Eisman J. A. Osteoarthritis, bone density, postural stability, and osteoporotic fractures: a population based study. J Rheumatol. 1995 May;22(5):921–925. [PubMed] [Google Scholar]
  17. Kirwan J. R., Silman A. J. Epidemiological, sociological and environmental aspects of rheumatoid arthritis and osteoarthrosis. Baillieres Clin Rheumatol. 1987 Dec;1(3):467–489. doi: 10.1016/s0950-3579(87)80041-9. [DOI] [PubMed] [Google Scholar]
  18. Kleerekoper M., Nelson D. A., Peterson E. L., Flynn M. J., Pawluszka A. S., Jacobsen G., Wilson P. Reference data for bone mass, calciotropic hormones, and biochemical markers of bone remodeling in older (55-75) postmenopausal white and black women. J Bone Miner Res. 1994 Aug;9(8):1267–1276. doi: 10.1002/jbmr.5650090817. [DOI] [PubMed] [Google Scholar]
  19. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  20. Lane N. E., Nevitt M. C. Osteoarthritis and bone mass. J Rheumatol. 1994 Aug;21(8):1393–1396. [PubMed] [Google Scholar]
  21. Linsenmayer T. F., Gibney E., Igoe F., Gordon M. K., Fitch J. M., Fessler L. I., Birk D. E. Type V collagen: molecular structure and fibrillar organization of the chicken alpha 1(V) NH2-terminal domain, a putative regulator of corneal fibrillogenesis. J Cell Biol. 1993 Jun;121(5):1181–1189. doi: 10.1083/jcb.121.5.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Manolagas S. C., Jilka R. L. Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med. 1995 Feb 2;332(5):305–311. doi: 10.1056/NEJM199502023320506. [DOI] [PubMed] [Google Scholar]
  23. Mansell J. P., Tarlton J. F., Bailey A. J. Biochemical evidence for altered subchondral bone collagen metabolism in osteoarthritis of the hip. Br J Rheumatol. 1997 Jan;36(1):16–19. doi: 10.1093/rheumatology/36.1.16. [DOI] [PubMed] [Google Scholar]
  24. Mansell J. P., Tarlton J. F., Bailey A. J. Expression of gelatinases within the trabecular bone compartment of ovariectomized and parathyroidectomized adult female rats. Bone. 1997 Jun;20(6):533–538. doi: 10.1016/s8756-3282(97)00034-3. [DOI] [PubMed] [Google Scholar]
  25. Marcelli C., Favier F., Kotzki P. O., Ferrazzi V., Picot M. C., Simon L. The relationship between osteoarthritis of the hands, bone mineral density, and osteoporotic fractures in elderly women. Osteoporos Int. 1995;5(5):382–388. doi: 10.1007/BF01622261. [DOI] [PubMed] [Google Scholar]
  26. Milgram J. W., Jasty M. Osteopetrosis. A morphological study of twenty-one cases. J Bone Joint Surg Am. 1982 Jul;64(6):912–929. [PubMed] [Google Scholar]
  27. Nefussi J. R., Pouchelet M., Collin P., Sautier J. M., Develay G., Forest N. Microcinematographic and autoradiographic kinetic studies of bone cell differentiation in vitro: matrix formation and mineralization. Bone. 1989;10(5):345–352. doi: 10.1016/8756-3282(89)90131-2. [DOI] [PubMed] [Google Scholar]
  28. Nelson D. A., Jacobsen G., Barondess D. A., Parfitt A. M. Ethnic differences in regional bone density, hip axis length, and lifestyle variables among healthy black and white men. J Bone Miner Res. 1995 May;10(5):782–787. doi: 10.1002/jbmr.5650100515. [DOI] [PubMed] [Google Scholar]
  29. Ohuchi E., Imai K., Fujii Y., Sato H., Seiki M., Okada Y. Membrane type 1 matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules. J Biol Chem. 1997 Jan 24;272(4):2446–2451. doi: 10.1074/jbc.272.4.2446. [DOI] [PubMed] [Google Scholar]
  30. Pead M. J., Skerry T. M., Lanyon L. E. Direct transformation from quiescence to bone formation in the adult periosteum following a single brief period of bone loading. J Bone Miner Res. 1988 Dec;3(6):647–656. doi: 10.1002/jbmr.5650030610. [DOI] [PubMed] [Google Scholar]
  31. Pfeilschifter J., Wolf O., Naumann A., Minne H. W., Mundy G. R., Ziegler R. Chemotactic response of osteoblastlike cells to transforming growth factor beta. J Bone Miner Res. 1990 Aug;5(8):825–830. doi: 10.1002/jbmr.5650050805. [DOI] [PubMed] [Google Scholar]
  32. Radin E. L., Abernethy P. J., Townsend P. M., Rose R. M. The role of bone changes in the degeneration of articular cartilage in osteoarthrosis. Acta Orthop Belg. 1978 Jan-Feb;44(1):55–63. [PubMed] [Google Scholar]
  33. Radin E. L., Rose R. M. Role of subchondral bone in the initiation and progression of cartilage damage. Clin Orthop Relat Res. 1986 Dec;(213):34–40. [PubMed] [Google Scholar]
  34. Reimann I., Mankin H. J., Trahan C. Quantitative histologic analyses of articular cartilage and subchondral bone from osteoarthritic and normal human hips. Acta Orthop Scand. 1977 May;48(1):63–73. doi: 10.3109/17453677708985113. [DOI] [PubMed] [Google Scholar]
  35. Rifas L., Fausto A., Scott M. J., Avioli L. V., Welgus H. G. Expression of metalloproteinases and tissue inhibitors of metalloproteinases in human osteoblast-like cells: differentiation is associated with repression of metalloproteinase biosynthesis. Endocrinology. 1994 Jan;134(1):213–221. doi: 10.1210/endo.134.1.8275936. [DOI] [PubMed] [Google Scholar]
  36. Risteli J., Risteli L. Analysing connective tissue metabolites in human serum. Biochemical, physiological and methodological aspects. J Hepatol. 1995;22(2 Suppl):77–81. [PubMed] [Google Scholar]
  37. Rodan G. A. Mechanical loading, estrogen deficiency, and the coupling of bone formation to bone resorption. J Bone Miner Res. 1991 Jun;6(6):527–530. doi: 10.1002/jbmr.5650060602. [DOI] [PubMed] [Google Scholar]
  38. Roholl P. J., Blauw E., Zurcher C., Dormans J. A., Theuns H. M. Evidence for a diminished maturation of preosteoblasts into osteoblasts during aging in rats: an ultrastructural analysis. J Bone Miner Res. 1994 Mar;9(3):355–366. doi: 10.1002/jbmr.5650090310. [DOI] [PubMed] [Google Scholar]
  39. Rubin C. T., Lanyon L. E. Regulation of bone mass by mechanical strain magnitude. Calcif Tissue Int. 1985 Jul;37(4):411–417. doi: 10.1007/BF02553711. [DOI] [PubMed] [Google Scholar]
  40. Sato H., Takino T., Okada Y., Cao J., Shinagawa A., Yamamoto E., Seiki M. A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature. 1994 Jul 7;370(6484):61–65. doi: 10.1038/370061a0. [DOI] [PubMed] [Google Scholar]
  41. Seibel M. J., Duncan A., Robins S. P. Urinary hydroxy-pyridinium crosslinks provide indices of cartilage and bone involvement in arthritic diseases. J Rheumatol. 1989 Jul;16(7):964–970. [PubMed] [Google Scholar]
  42. Sims T. J., Bailey A. J. Quantitative analysis of collagen and elastin cross-links using a single-column system. J Chromatogr. 1992 Nov 6;582(1-2):49–55. doi: 10.1016/0378-4347(92)80301-6. [DOI] [PubMed] [Google Scholar]
  43. Sowers M. F., Hochberg M., Crabbe J. P., Muhich A., Crutchfield M., Updike S. Association of bone mineral density and sex hormone levels with osteoarthritis of the hand and knee in premenopausal women. Am J Epidemiol. 1996 Jan 1;143(1):38–47. doi: 10.1093/oxfordjournals.aje.a008655. [DOI] [PubMed] [Google Scholar]

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