Cohen Jordan S, Fung Ashley K, Stein Matthew K, Darrieutort-Laffite Christelle, Weiss Stephanie N, Shetye Snehal S, Thurlow Nat A, Nuss Courtney A, Dyment Nathaniel A, Soslowsky Louis J
McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, USA.
INSERM, Regenerative Medicine and Skeleton, RMeS, UMR 1229, Nantes Université, Oniris, CHU Nantes, Nantes, France.
Connect Tissue Res. 2024 Nov;65(6):497-510. doi: 10.1080/03008207.2024.2432324. Epub 2024 Dec 2.
Collagen XI is a fibril-forming collagen typically associated with type II collagen tissues but is also expressed in type I collagen-rich tendons, especially during development. We previously showed that tendon-targeted (Scx-Cre) Col11a1 knockout mice have smaller tendons in adulthood with aberrant fibril structure and impaired mechanical properties. However, the manifestation of this phenotype is not clearly understood. Therefore, our objective is to define the spatiotemporal roles of collagen XI in tendon structure-function during postnatal development. Given the high expression of collagen XI during embryonic development, we hypothesized that collagen XI knockout leads to the deposition of weakened extracellular matrix during early postnatal timepoints, disrupting the establishment of tendon structure and function.
Patellar and Achilles tendons from postnatal (P) days 0, 10, 20, and 30 tendon-targeted scleraxis-Cre heterozygous and homozygous Col11a1 knockout mice were evaluated for morphology, nuclear organization, fibril morphology, mechanical properties, and gene expression.
At P0, there were no differences in tendon length or fibril diameter of either tendon. By P10, striking structural and functional differences emerged, with collagen XI deficiency resulting in increased tendon length, a heterogeneous and larger diameter population of fibrils, and inferior mechanical properties in both patellar and Achilles tendons. Differences increased in magnitude through P30, supporting our hypothesis that impaired structure-function during postnatal development may drive tendon lengthening and reduced mechanical properties.
Though collagen XI is a quantitatively minor component of the tendon extracellular matrix, these results highlight the critical role of collagen XI in the acquisition of tendon structure-function.
胶原蛋白XI是一种形成纤维的胶原蛋白，通常与II型胶原组织相关，但也在富含I型胶原的肌腱中表达，尤其是在发育过程中。我们之前发现，肌腱靶向（Scx-Cre）Col11a1基因敲除小鼠成年后肌腱较小，纤维结构异常，力学性能受损。然而，这种表型的表现尚不清楚。因此，我们的目标是确定出生后发育过程中胶原蛋白XI在肌腱结构功能中的时空作用。鉴于胚胎发育期间胶原蛋白XI的高表达，我们推测胶原蛋白XI基因敲除会导致出生后早期细胞外基质沉积减弱，从而破坏肌腱结构和功能的建立。
对出生后（P）0天、10天、20天和30天的肌腱靶向硬骨素-Cre杂合子和纯合子Col11a1基因敲除小鼠的髌腱和跟腱进行形态学、核组织、纤维形态、力学性能和基因表达评估。
在P0时，两种肌腱的长度或纤维直径均无差异。到P10时，出现了显著的结构和功能差异，胶原蛋白XI缺乏导致肌腱长度增加，纤维群体直径不均一且更大，髌腱和跟腱的力学性能均较差。差异在P30时进一步增大，支持了我们的假设，即出生后发育过程中结构功能受损可能导致肌腱延长和力学性能降低。
尽管胶原蛋白XI在肌腱细胞外基质中含量较少，但这些结果突出了胶原蛋白XI在肌腱结构功能形成中的关键作用。
