Thyroid hormone enhances aggrecanase-2/ADAM-TS5 expression and proteoglycan degradation in growth plate cartilage.

Effects of thyroid hormone on proteoglycan degradation in various regions of cartilage were investigated. In propylthiouracil-treated rats with hypothyroidism, proteoglycan degradation in epiphyseal cartilage during endochondral ossification was markedly suppressed. However, injections of T(4) reversed this effect of propylthiouracil on proteoglycan degradation. In pig growth plate explants, T(3) also induced breakdown of proteoglycan. T(3) increased the release of aggrecan monomer and core protein from the explants into the medium. Accordingly, the level of aggrecan monomer remaining in the tissue decreased after T(3) treatment, and the monomer lost hyaluronic acid-binding capacity, suggesting that the cleavage site is in the interglobular domain. The aggrecan fragment released from the T(3)-exposed explants underwent cleavage at Glu(373)-Ala(374), the major aggrecanase-cleavage site. The stimulation of proteoglycan degradation by T(3) was less prominent in resting cartilage explants than in growth plate explants and was barely detectable in articular cartilage explants. Using rabbit growth plate chondrocyte cultures, we explored proteases that may be involved in T(3)-induced aggrecan degradation and found that T(3) enhanced the expression of aggrecanase-2/ADAM-TS5 (a disintegrin and a metalloproteinase domain with thrombospondin type I domains) mRNA, whereas we could not detect any enhancement of stromelysin, gelatinase, or collagenase activities or any aggrecanase-1/ADAM-TS4 mRNA expression. We also found that the aggrecanse-2 mRNA level, but not aggrecanase-1, increased at the hypertrophic stage during endochondral ossification. These findings suggest that aggrecanse-2/ADAM-TS5 is involved in aggrecan breakdown during endochondral ossification, and that thyroid hormone stimulates the aggrecan breakdown partly via the enhancement of aggrecanase-2/ADAM-TS5.

[1]  T. Aigner,et al.  Relative messenger RNA expression profiling of collagenases and aggrecanases in human articular chondrocytes in vivo and in vitro. , 2002, Arthritis and rheumatism.

[2]  P. Yen,et al.  Physiological and molecular basis of thyroid hormone action. , 2001, Physiological reviews.

[3]  T. Kawamoto,et al.  Direct inhibition of Indian hedgehog expression by parathyroid hormone (PTH)/PTH-related peptide and up-regulation by retinoic acid in growth plate chondrocyte cultures. , 2001, Experimental cell research.

[4]  D. Stevens,et al.  Thyroid Hormones Regulate Hypertrophic Chondrocyte Differentiation and Expression of Parathyroid Hormone‐Related Peptide and Its Receptor During Endochondral Bone Formation , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[5]  P. Billings,et al.  MMP‐13 is induced during chondrocyte hypertrophy , 2000, Journal of cellular biochemistry.

[6]  R. W. Rauser,et al.  Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[7]  R. Wynn,et al.  Cloning and Characterization of ADAMTS11, an Aggrecanase from the ADAMTS Family* , 1999, The Journal of Biological Chemistry.

[8]  R. Wynn,et al.  Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins. , 1999, Science.

[9]  A. Rowan,et al.  The Regulation of MMPs and TIMPs in Cartilage Turnover , 1999, Annals of the New York Academy of Sciences.

[10]  J. Trzăskos,et al.  Generation and Characterization of Aggrecanase , 1999, The Journal of Biological Chemistry.

[11]  J. Samarut,et al.  Different functions for the thyroid hormone receptors TRα and TRβ in the control of thyroid hormone production and post‐natal development , 1999 .

[12]  H. Seo,et al.  Thyroid hormone action on liver, heart, and energy expenditure in thyroid hormone receptor beta-deficient mice. , 1998, Endocrinology.

[13]  B. Genge,et al.  Thyroid Hormone Inhibits Growth and Stimulates Terminal Differentiation of Epiphyseal Growth Plate Chondrocytes , 1998, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[14]  M. Itoman,et al.  Thyroid hormone-induced chondrocyte terminal differentiation in rat femur organ culture , 1998, Cell and Tissue Research.

[15]  T. Kawamoto,et al.  Effects of Parathyroid Hormone (PTH) and PTH-Related Peptide on Expressions of Matrix Metalloproteinase- 2, -3, and -9 in Growth Plate Chondrocyte Cultures. , 1998, Endocrinology.

[16]  Frank Baas,et al.  Abnormal heart rate and body temperature in mice lacking thyroid hormone receptor α1 , 1998, The EMBO journal.

[17]  T. Kawamoto,et al.  Effects of parathyroid hormone (PTH) and PTH-related peptide on expressions of matrix metalloproteinase-2, -3, and -9 in growth plate chondrocyte cultures. , 1998, Endocrinology.

[18]  J. Wit,et al.  Catch-up growth. , 1997, Endocrine reviews.

[19]  C. Dehay,et al.  The T 3 R α gene encoding a thyroid hormone receptor is essential for post-natal development and thyroid hormone production mediate ligand-dependent transcriptional control of target , 1997 .

[20]  R. Weiss,et al.  Effect of thyroid hormone on growth. Lessons from the syndrome of resistance to thyroid hormone. , 1996, Endocrinology and metabolism clinics of North America.

[21]  D. Forrest,et al.  Thyroid hormone receptor β is essential for development of auditory function , 1996, Nature Genetics.

[22]  D. Forrest,et al.  Recessive resistance to thyroid hormone in mice lacking thyroid hormone receptor beta: evidence for tissue‐specific modulation of receptor function. , 1996, The EMBO journal.

[23]  A. Poole,et al.  In serum‐free culture thyroid hormones can induce full expression of chondrocyte hypertrophy leading to matrix calcification , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[24]  J. Weidner,et al.  Cell-mediated Catabolism of Aggrecan , 1995, The Journal of Biological Chemistry.

[25]  A. Reddi,et al.  Thyroxine is the serum factor that regulates morphogenesis of columnar cartilage from isolated chondrocytes in chemically defined medium , 1994, The Journal of cell biology.

[26]  M. Takigawa,et al.  Changes in parathyroid hormone receptors during chondrocyte cytodifferentiation. , 1994, The Journal of biological chemistry.

[27]  M. Glade,et al.  Insulin and thyroid hormones stimulate matrix metabolism in primary cultures of articular chondrocytes from young rabbits independently and in combination. , 1994, Connective tissue research.

[28]  M. Iwamoto,et al.  Characterization of the mineralization process in cultures of rabbit growth plate chondrocytes. , 1993, Developmental biology.

[29]  R. Cancedda,et al.  Thyroid hormone, insulin, and glucocorticoids are sufficient to support chondrocyte differentiation to hypertrophy: a serum-free analysis , 1992, The Journal of cell biology.

[30]  K. Naka,et al.  Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080 human fibrosarcoma cells. Purification and activation of the precursor and enzymic properties. , 1992, The Journal of biological chemistry.

[31]  T. Hardingham,et al.  The interglobular domain of cartilage aggrecan is cleaved by PUMP, gelatinases, and cathepsin B. , 1992, The Journal of biological chemistry.

[32]  G. Homandberg,et al.  Fibronectin fragments cause chondrolysis of bovine articular cartilage slices in culture. , 1992, The Journal of biological chemistry.

[33]  T. Tschan,et al.  Induction of proliferation or hypertrophy of chondrocytes in serum-free culture: the role of insulin-like growth factor-I, insulin, or thyroxine , 1992, The Journal of cell biology.

[34]  J. Sandy,et al.  Catabolism of aggrecan in cartilage explants. Identification of a major cleavage site within the interglobular domain. , 1991, The Journal of biological chemistry.

[35]  K. Nakashima,et al.  Effects of parathyroid hormone and calcitonin on alkaline phosphatase activity and matrix calcification in rabbit growth-plate chondrocyte cultures. , 1990, Endocrinology.

[36]  K. Iwata,et al.  Rapid one-step sandwich enzyme immunoassay for tissue inhibitor of metalloproteinases. An application for rheumatoid arthritis serum and plasma. , 1990, Journal of immunological methods.

[37]  E. Lebenthal,et al.  Thyroidal regulation of rat pancreatic nuclear triiodothyronine receptor during postnatal development. , 1990, Endocrinology.

[38]  Y. Okada,et al.  Activation of matrix metalloproteinase 3 (stromelysin) and matrix metalloproteinase 2 (‘gelatinase’) by human neutrophil elastase and cathepsin G , 1989, FEBS letters.

[39]  P. Roughley,et al.  Degradation of proteoglycan aggregate by a cartilage metalloproteinase. Evidence for the involvement of stromelysin in the generation of link protein heterogeneity in situ. , 1989, The Biochemical journal.

[40]  Z. Hochberg,et al.  Effect of thyroid hormone and growth hormone on recovery from hypothyroidism of epiphyseal growth plate cartilage and its adjacent bone. , 1989, Endocrinology.

[41]  M. Iwamoto,et al.  Terminal differentiation and calcification in rabbit chondrocyte cultures grown in centrifuge tubes: regulation by transforming growth factor beta and serum factors. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[42]  S. Rivkees,et al.  Long-term growth in juvenile acquired hypothyroidism: the failure to achieve normal adult stature. , 1987, The New England journal of medicine.

[43]  R. Evans,et al.  The c-erb-A gene encodes a thyroid hormone receptor , 1986, Nature.

[44]  H. Beug,et al.  The c-erb-A protein is a high-affinity receptor for thyroid hormone , 1986, Nature.

[45]  Y. Okada,et al.  A metalloproteinase from human rheumatoid synovial fibroblasts that digests connective tissue matrix components. Purification and characterization. , 1986, The Journal of biological chemistry.

[46]  D. Gospodarowicz,et al.  Effect of exogenous extracellular matrices on proteoglycan synthesis by cultured rabbit costal chondrocytes , 1985, The Journal of cell biology.

[47]  V. Hascall,et al.  Turnover of proteoglycans in cultures of bovine articular cartilage. , 1984, Archives of biochemistry and biophysics.

[48]  H Ide,et al.  Limb bud chondrogenesis in cell culture, with particular reference to serum concentration in the culture medium. , 1984, Experimental cell research.

[49]  H. Moor,et al.  Cartilage ultrastructure after high pressure freezing, freeze substitution, and low temperature embedding. I. Chondrocyte ultrastructure--implications for the theories of mineralization and vascular invasion , 1984, The Journal of cell biology.

[50]  H. C. Robinson,et al.  The effect of serum on biosynthesis of proteoglycans by bovine articular cartilage in culture. , 1983, Archives of biochemistry and biophysics.

[51]  L. Philipson,et al.  Regulation of glycosaminoglycan synthesis by thyroid hormone in vitro. , 1982, The Journal of clinical investigation.

[52]  H. Lebovitz,et al.  Triiodothyronine stimulation of in vitro growth and maturation of embryonic chick cartilage. , 1982, Endocrinology.

[53]  J. Kimura,et al.  The ultrastructure of cultures from the swarm rat chondrosarcoma , 1981, The Anatomical record.

[54]  S. Refetoff,et al.  The effect of thyroid hormone on glycosaminoglycan accumulation in human skin fibroblasts. , 1981, Endocrinology.

[55]  K. Gibson,et al.  Stimulation of proteoglycan synthesis in chick embryo sternum by serum and L-3,5,3'-triiodothyronine. , 1976, The Journal of biological chemistry.

[56]  D. Heinegård,et al.  Characterization of chondroitin sulfate isolated from trypsin-chymotrypsin digests of cartilage proteoglycans. , 1974, Archives of biochemistry and biophysics.

[57]  S. Krane,et al.  An endopeptidase from rheumatoid synovial tissue culture. , 1972, Biochimica et biophysica acta.

[58]  V. Matukas,et al.  EVIDENCE FOR CHANGES IN PROTEIN POLYSACCHARIDE ASSOCIATED WITH THE ONSET OF CALCIFICATION IN CARTILAGE , 1968, The Journal of cell biology.

[59]  A. Jibril.  Proteolytic degradation of ossifying cartilage matrix and the removal of acid mucopolysaccharides prior to bone formation. , 1967, Biochimica et biophysica acta.

[60]  A. Hirschman,et al.  Protein- Polysaccharide Loss during Endochondral Ossification: Immunochemical Evidence , 1966, Science.

[61]  T BITTER,et al.  A modified uronic acid carbazole reaction. , 1962, Analytical biochemistry.