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.
Department of Prosthetic Dentistry, Hiroshima University Faculty of Dentistry, Minami-ku, Hiroshima 734-8553, Japan. smakihara@forsyth.org
Seicho
S
Makihira
Weiqun
W
Yan
Hiroshi
H
Murakami
Masae
M
Furukawa
Toshihisa
T
Kawai
Hiroki
H
Nikawa
Eri
E
Yoshida
Taizo
T
Hamada
Yasunori
Y
Okada
Yukio
Y
Kato
D051722:ADAM Proteins; D000071121:ADAMTS4 Protein; D000367:Age Factors; D000818:Animals; D002356:Cartilage / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000201:enzymology*; D017364:Collagenases / Q000378:metabolism; D003470:Culture Media / Q000378:metabolism; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D006132:Growth Plate / Q000166:cytology / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism; D011247:Pregnancy; D011348:Procollagen N-Endopeptidase; D011509:Proteoglycans / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D051381:Rats; D013552:Swine; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*; D014574:Uronic Acids / Q000378:metabolism
D003470:Culture Media; D007375:Interleukin-1; D010446:Peptide Fragments; D011509:Proteoglycans; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D014574:Uronic Acids; D014284:Triiodothyronine; D051722:ADAM Proteins; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D011348:Procollagen N-Endopeptidase; D019278:Matrix Metalloproteinase 3; D000071121:ADAMTS4 Protein