| 論文種別 | 原著(症例報告除く) |
| 言語種別 | 英語 |
| 査読の有無 | その他(不明) |
| 表題 | Fibulin-4 is required for the mechanical stability of tendons. |
| 掲載誌名 | 正式名：Cell and tissue research 略 称：Cell Tissue Res ISSNコード：14320878/0302766X |
| 掲載区分 | 国外 |
| 巻・号・頁 | pp.Online ahead of print |
| 著者・共著者 | Takako Sasaki, Kyoko Jin, Aki Takimoto, Yuki Taga, Yoshihiro Ishikawa, Hans Peter Bächinger, Takao Sakai, Takeshi Terabayashi, Katsuhiro Hanada, Ursula Schlötzer-Schrehardt, Chisa Shukunami, Yuji Hiraki, Tomoyuki Nakamura, Ei Yamamoto |
| 発行年月 | 2025/11 |
| 概要 | Fibulin-4, an extracellular matrix protein, is indispensable for elastic fiber assembly. Fibulin-4 null mice show bilateral forelimb contracture and patients with EFEMP2/FBLN4 mutations demonstrate similar defects, besides joint laxity, vascular and pulmonary abnormalities. Here we report that limb tendons in fibulin-4 null mice developed normally until E17.5-18.5, but thereafter thinner tendons showed abnormalities, suggesting that fibulin-4 maintains the integrity of certain tendons. Tendon/ligament specific conditional knockout mice of Efemp2/Fbln4 (ScxCre-H;Fbln4flox/- mice) were generated in order to elucidate its role of collagen fibril organization, collagen cross-linking and mechanical features of tendons. Curiously, however, the conditional Fbln4 knockout mice did not show forelimb contractures or other obvious morphological defects. We could detect small amounts of fibulin-4 in tendon extracts, but isolated tenocytes from the conditional knockout mice did not secrete fibulin-4, confirming that the Efemp2/Fbln4 gene was properly deleted in tenocytes. Electron microscopic analyses revealed an enhanced proportion of thinner fibrils in tendons from the conditional knockout mice. Furthermore, mechanical stress tests of patellar tendons of the conditional knockout mice revealed strongly reduced strain resistance compared to the tendons of control mice, although cross-link formation and thermal stability of tendon collagen were not affected. These finding indicate that fibulin-4 has an important role in the organization and stability of collagen fibrils in tendons. |
| DOI | 10.1007/s00441-025-04028-3 |
| PMID | 41231259 |