Loss of Smad4 in the scleraxis cell lineage results in postnatal joint contracture.

Loss of Smad4 in the scleraxis cell lineage results in postnatal joint contracture.
Dev Biol. 2020 Nov 25;:
Authors: Schlesinger S, Seo S, Pryce B, Tufa SF, Keene DR, Huang AH, Schweitzer R
Abstract
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). Smad4ScxCre mutants develop a joint contracture shortly after birth. The contracture is stochastic in direction and increases in severity with age. Smad4ScxCre mutant tendons exhibited a stable reduction in cellularity and a progressive reduction in extracellular matrix volume. Collagen fibril diameters were reduced in the Smad4ScxCre 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; 3ScxCre mutants did not result in joint contractures. Conversely, disrupting the BMP pathway by targeting BMP receptors (Alk3ScxCre/Alk6null) recapitulat...

Source: Developmental Biology - November 25, 2020 Category: Biology Authors: Schlesinger S, Seo S, Pryce B, Tufa SF, Keene DR, Huang AH, Schweitzer R Tags: Dev Biol Source Type: research