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Molecular and Cellular Biology, January 2005, p. 699-705, Vol. 25, No. 2
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.2.699-705.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Tenomodulin Is Necessary for Tenocyte Proliferation and Tendon Maturation

Denitsa Docheva,1 Ernst B. Hunziker,2 Reinhard Fässler,1* and Oliver Brandau1,{dagger}

Department of Molecular Medicine, Max Planck Institute for Biochemistry, Martinsried, Germany,1 ITI Research Institute, University of Berne, Berne, Switzerland2

Received 15 October 2004/ Accepted 26 October 2004

Tenomodulin (Tnmd) is a member of a new family of type II transmembrane glycoproteins. It is predominantly expressed in tendons, ligaments, and eyes, whereas the only other family member, chondromodulin I (ChM-I), is highly expressed in cartilage and at lower levels in the eye and thymus. The C-terminal extracellular domains of both proteins were shown to modulate endothelial-cell proliferation and tube formation in vitro and in vivo. We analyzed Tnmd function in vivo and provide evidence that Tnmd is processed in vivo and that the proteolytically cleaved C-terminal domain can be found in tendon extracts. Loss of Tnmd expression in gene targeted mice abated tenocyte proliferation and led to a reduced tenocyte density. The deposited amounts of extracellular matrix proteins, including collagen types I, II, III, and VI and decorin, lumican, aggrecan, and matrilin-2, were not affected, but the calibers of collagen fibrils varied significantly and exhibited increased maximal diameters. Tnmd-deficient mice did not have changes in tendon vessel density, and mice lacking both Tnmd and ChM-I had normal retinal vascularization and neovascularization after oxygen-induced retinopathy. These results suggest that Tnmd is a regulator of tenocyte proliferation and is involved in collagen fibril maturation but do not confirm an in vivo involvement of Tnmd in angiogenesis.


* Corresponding author. Mailing address: Max Planck Institute for Biochemistry, Department of Molecular Medicine, Am Klopferspitz 18, 82152 Martinsried, Germany. Phone: 49-89-8578-2424. Fax: 49-89-8578-2422. E-mail: faessler{at}biochem.mpg.de.

{dagger} Present address: Department of Physiology, LMU-München, 80336 Munich, Germany.


Molecular and Cellular Biology, January 2005, p. 699-705, Vol. 25, No. 2
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.2.699-705.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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