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

Seicho Makihira, Weiqun Yan, Hiroshi Murakami, Masae Furukawa, Toshihisa Kawai, Hiroki Nikawa, Eri Yoshida, Taizo Hamada, Yasunori Okada, Yukio Kato

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Abstract

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 T4 reversed this effect of propylthiouracil on proteoglycan degradation. In pig growth plate explants, T3 also induced breakdown of proteoglycan. T3 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 T3 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 T3-exposed explants underwent cleavage at Glu373-Ala374, the major aggrecanase-cleavage site. The stimulation of proteoglycan degradation by T3 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 T3-induced aggrecan degradation and found that T3 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.

Original languageEnglish
Pages (from-to)2480-2488
Number of pages9
JournalEndocrinology
Volume144
Issue number6
DOIs
Publication statusPublished - 2003 Jun 1

Fingerprint

Aggrecans
Growth Plate
Proteoglycans
Thyroid Hormones
Cartilage
Osteogenesis
Propylthiouracil
Messenger RNA
Thrombospondins
Disintegrins
Matrix Metalloproteinase 3
Gelatinases
Articular Cartilage
Metalloproteases
Collagenases
Hyaluronic Acid
Chondrocytes
Hypothyroidism
ADAMTS5 Protein
Peptide Hydrolases

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Makihira, S., Yan, W., Murakami, H., Furukawa, M., Kawai, T., Nikawa, H., ... Kato, Y. (2003). Thyroid hormone enhances aggrecanase-2/ADAM-TS5 expression and proteoglycan degradation in growth plate cartilage. Endocrinology, 144(6), 2480-2488. https://doi.org/10.1210/en.2002-220746

Thyroid hormone enhances aggrecanase-2/ADAM-TS5 expression and proteoglycan degradation in growth plate cartilage. / Makihira, Seicho; Yan, Weiqun; Murakami, Hiroshi; Furukawa, Masae; Kawai, Toshihisa; Nikawa, Hiroki; Yoshida, Eri; Hamada, Taizo; Okada, Yasunori; Kato, Yukio.

In: Endocrinology, Vol. 144, No. 6, 01.06.2003, p. 2480-2488.

Research output: Contribution to journalArticle

Makihira, S, Yan, W, Murakami, H, Furukawa, M, Kawai, T, Nikawa, H, Yoshida, E, Hamada, T, Okada, Y & Kato, Y 2003, 'Thyroid hormone enhances aggrecanase-2/ADAM-TS5 expression and proteoglycan degradation in growth plate cartilage', Endocrinology, vol. 144, no. 6, pp. 2480-2488. https://doi.org/10.1210/en.2002-220746
Makihira, Seicho ; Yan, Weiqun ; Murakami, Hiroshi ; Furukawa, Masae ; Kawai, Toshihisa ; Nikawa, Hiroki ; Yoshida, Eri ; Hamada, Taizo ; Okada, Yasunori ; Kato, Yukio. / Thyroid hormone enhances aggrecanase-2/ADAM-TS5 expression and proteoglycan degradation in growth plate cartilage. In: Endocrinology. 2003 ; Vol. 144, No. 6. pp. 2480-2488.
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