Growth of the musculoskeletal system requires precise coordination between bone, muscle, and tendon during development. Insufficient elongation of the muscle-tendon unit relative to bone growth results in joint contracture, a condition characterized by reduction or complete loss of joint range of motion. Here we establish a novel murine model of joint contracture by targeting Smad4 for deletion in the tendon cell lineage using Scleraxis-Cre (ScxCre). Smad4^ScxCre mutants develop a joint contracture shortly after birth. The contracture is stochastic in direction and increases in severity with age. Smad4^ScxCre mutant tendons exhibited a stable reduction in cellularity and a progressive reduction in extracellular matrix volume. Collagen fibril diameters were reduced in the Smad4^ScxCre mutants, suggesting a role for Smad4 signaling in the regulation of matrix accumulation. Although ScxCre also has sporadic activity in both cartilage and muscle, we demonstrate an essential role for Smad4 loss in tendons for the development of joint contractures. Disrupting the canonical TGFβ-pathway in Smad2;3^ScxCre mutants did not result in joint contractures. Conversely, disrupting the BMP pathway by targeting BMP receptors (Alk3^ScxCre/Alk6^null) recapitulated many features of the Smad4^ScxCre contracture phenotype, suggesting that joint contracture in Smad4^ScxCre mutants is caused by disruption of BMP signaling. Overall, these results establish a model of murine postnatal joint contracture and a role for BMP signaling in tendon elongation and extracellular matrix accumulation.

肌肉骨骼系统的生长需要在发育过程中骨骼、肌肉和肌腱之间的精确协调。肌肉-肌腱单元相对于骨骼生长的伸长不足会导致关节挛缩，这种情况的特征是关节活动范围减少或完全丧失。在这里，我们通过使用 Scleraxis-Cre (ScxCre) 靶向 Smad4 在肌腱细胞谱系中缺失来建立一种新的小鼠关节挛缩模型。Smad4 ^ScxCre突变体在出生后不久就会出现关节挛缩。挛缩的方向是随机的，并且随着年龄的增长而加重。Smad4 ^ScxCre突变肌腱表现出细胞数量的稳定减少和细胞外基质体积的逐渐减少。Smad4 中的胶原原纤维直径减小^ScxCre突变体，表明 Smad4 信号传导在调节基质积累中的作用。尽管 ScxCre 在软骨和肌肉中也有零星的活动，但我们证明了 Smad4 在肌腱中的缺失对关节挛缩的发展具有重要作用。^{破坏 Smad2;3 ScxCre}突变体中的经典 TGFβ 通路不会导致关节挛缩。相反，通过靶向 BMP 受体（Alk3 ^ScxCre /Alk6 ^{null ）破坏 BMP 通路，概括了 Smad4 ScxCre}挛缩表型的许多特征，表明 Smad4 ^{ScxCre中的关节挛缩}突变体是由 BMP 信号的中断引起的。总体而言，这些结果建立了小鼠产后关节挛缩模型以及 BMP 信号在肌腱伸长和细胞外基质积累中的作用。