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Localization of Smads, the TGF‐β Family Intracellular Signaling Components During Endochondral Ossification
Author(s) -
Sakou Takashi,
Onishi Toshiyuki,
Yamamoto Takuya,
Nagamine Tomonori,
Sampath T. Kuber,
ten Dijke Peter
Publication year - 1999
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1999.14.7.1145
Subject(s) - smad , bone morphogenetic protein , endochondral ossification , microbiology and biotechnology , r smad , receptor , smad2 protein , activin type 2 receptors , signal transduction , transforming growth factor beta , transforming growth factor , biology , bone morphogenetic protein 10 , chondrocyte , chemistry , bmpr2 , medicine , endocrinology , tgf beta signaling pathway , cartilage , bone morphogenetic protein 7 , growth factor , anatomy , tgf alpha , biochemistry , gene
Members of the transforming growth factor‐β (TGF‐β) family transduce signals from the cell membrane to the nucleus via specific type I and type II receptors and Smad proteins. Smad1 and Smad5 mediate intracellular signaling of bone morphogenetic protein (BMP), whereas Smad2 and Smad3 transduce TGF‐β signaling. Smad4 is a common mediator required for both pathways. Smad6 and Smad7 inhibit signaling by members of the TGF‐β superfamily. Here, we examined the expression of Smad1 to Smad7 proteins during endochondral ossification of epiphyseal plate of growing rats using immunohistochemical techniques. The expression of Smad proteins was correlated with the expression of TGF‐β1 and its receptors, and BMP‐2/4 and BMP receptors. The results show that TGF‐β1 and BMP‐2/4 were actively expressed in chondrocytes that are undergoing proliferation and maturation, which overlaps with expression of their corresponding type I and type II receptors. The Smads, however, exhibited a distinct expression pattern, respectively. For example, Smad1 and Smad5 were highly expressed in proliferating chondrocytes and in those chondrocytes that are undergoing maturation. The TGF‐β/activin‐restricted Smads were also expressed in a nearly complementary fashion; Smad2 was strongly expressed in proliferating chondrocytes, whereas Smad3 was strongly observed in maturing chondrocytes. Smad4 was broadly expressed in all zones of epiphyseal plate. Inhibitory Smads, Smad6 and Smad7, were strongly expressed in the zone of cartilage that contained mature chondrocytes. Our findings show a colocalization of the pathway‐restricted and inhibitory Smads with activating ligands or ligands whose action they antagonize and their receptors in various zones of epiphyseal growth plate, suggesting that TGF‐β superfamily Smad signaling pathways plays a morphogenic role during endochondral bone formation.