Tenomodulin is necessary for tenocyte proliferation and tendon maturation
Tenomodulin is necessary for tenocyte proliferation and tendon maturation
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DOI：
10.1128/mcb.25.2.699-705.2005
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发表时间：
2005-01-01
影响因子：
5.3
通讯作者：
Brandau, O
中科院分区：
文献类型：
--
作者：
Docheva, D;Hunziker, EB;Brandau, O
Tenomodulin（Tnmd）是一个新的II型跨膜糖蛋白家族的成员。它主要在肌腱、韧带和眼睛中表达，而唯一的另一个家族成员软骨调节素I（ChM-I）在软骨中高度表达，在眼睛和胸腺中表达水平较低。这两种蛋白质的C-末端胞外结构域被证明可以在体外和体内调节内皮细胞增殖和管形成。我们分析了Tnmd在体内的功能，并提供证据表明，Tnmd是在体内加工，蛋白水解裂解的C-末端结构域可以在肌腱提取物中找到。基因靶向小鼠中Tnmd表达的缺失减弱了腱细胞增殖并导致腱细胞密度降低。细胞外基质蛋白，包括胶原蛋白I型，II型，III型和IV型核心蛋白聚糖，光蛋白聚糖，聚集蛋白聚糖和matrilin-2的沉积量不受影响，但胶原纤维的口径变化显着，并表现出增加的最大直径。Tnmd缺陷小鼠的肌腱血管密度没有变化，缺乏Tnmd和ChM-I的小鼠在氧诱导的视网膜病变后具有正常的视网膜血管形成和新生血管形成。这些结果表明，Tnmd是肌腱细胞增殖的调节剂，并参与胶原纤维的成熟，但没有确认在体内参与血管生成的Tnmd。
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 IV 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.