Tenomodulin is necessary for tenocyte proliferation and tendon maturation.
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.
Docheva
Denitsa
D
Max Planck Institute for Biochemistry, Department of Molecular Medicine, Am Klopferspitz 18, 82152 Martinsried, Germany.
Hunziker
Ernst B
EB
Fässler
Reinhard
R
Brandau
Oliver
O
D000818:Animals; D000831:Animals, Newborn; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005260:Female; D018390:Gene Targeting; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009077:Mucins / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism; D015861:Retinal Neovascularization; D052116:Sialomucins; D013710:Tendons / Q000166:cytology* / Q000502:physiology*
D008565:Membrane Proteins; D009077:Mucins; D052116:Sialomucins; C486026:Tnmd protein, mouse; D003094:Collagen