Differential influence of quadriceps rate of torque development on single- and double-leg landing mechanics in anterior cruciate ligament reconstructed and control females.

PURPOSE: The capacity to explosively contract quadriceps within the critical timeframe associated with anterior cruciate ligament (ACL) injury, quantified by the rate of torque development, is potentially essential for safe landing mechanics. This study aimed to investigate the influence of explosive quadriceps strength on ACL-related sagittal-plane landing mechanics in females with and without ACL reconstruction (ACLR). METHODS: Quadriceps explosive strength and landing mechanics were assessed in 19 ACLR and 19 control females during isometric contractions and double- and single-leg jump landings. A stepwise multiple linear regression model determined the variance in each of the landing biomechanics variables for the ACLR limb and nondominant limb of controls that could be explained by the group, rate of torque development and/or their interaction. If peak kinetic variables could be predicted by the rate of torque development or interaction, additional analyses were conducted, accounting for knee flexion as a covariate in the regression model. RESULTS: During single-leg landings, ACLR females exhibited greater knee flexion at initial contact than controls (p = 0.04). Greater quadriceps rate of torque development predicted higher peak posterior ground reaction force and anterior tibial shear force in both groups (p = 0.04). However, after controlling for knee flexion angle at those peak forces, quadriceps rate of torque development was not predictive. In double-leg landings, greater explosive quadriceps strength was associated with quicker attainment of peak knee extension moment and posterior ground reaction force in the ACLR limb (p = 0.03). CONCLUSION: Regardless of ACL injury status, females with greater explosive quadriceps strength adopted safer single-leg landings through increased knee flexion, potentially mitigating ACL loading despite encountering higher peak forces. During double-leg landings, a greater explosive quadriceps strength of the ACLR limb is associated with faster achievement of peak force upon landing. Incorporating explosive quadriceps strengthening into post-ACLR rehabilitation and injury prevention programmes may enhance landing mechanics for reducing primary and subsequent ACL injury risks. LEVEL OF EVIDENCE: Level II.

TEM1/endosialin/CD248 promotes pathologic scarring and TGF-ß activity through its receptor stability in dermal fibroblasts.

BACKGROUND: Pathologic scars, including keloids and hypertrophic scars, represent a common form of exaggerated cutaneous scarring that is difficult to prevent or treat effectively. Additionally, the pathobiology of pathologic scars remains poorly understood. We aim at investigating the impact of TEM1 (also known as endosialin or CD248), which is a glycosylated type I transmembrane protein, on development of pathologic scars. METHODS: To investigate the expression of TEM1, we utilized immunofluorescence staining, Western blotting, and single-cell RNA-sequencing (scRNA-seq) techniques. We conducted in vitro cell culture experiments and an in vivo stretch-induced scar mouse model to study the involvement of TEM1 in TGF-ß-mediated responses in pathologic scars. RESULTS: The levels of the protein TEM1 are elevated in both hypertrophic scars and keloids in comparison to normal skin. A re-analysis of scRNA-seq datasets reveals that a major profibrotic subpopulation of keloid and hypertrophic scar fibroblasts greatly expresses TEM1, with expression increasing during fibroblast activation. TEM1 promotes activation, proliferation, and ECM production in human dermal fibroblasts by enhancing TGF-ß1 signaling through binding with and stabilizing TGF-ß receptors. Global deletion of Tem1 markedly reduces the amount of ECM synthesis and inflammation in a scar in a mouse model of stretch-induced pathologic scarring. The intralesional administration of ontuxizumab, a humanized IgG monoclonal antibody targeting TEM1, significantly decreased both the size and collagen density of keloids. CONCLUSIONS: Our data indicate that TEM1 plays a role in pathologic scarring, with its synergistic effect on the TGF-ß signaling contributing to dermal fibroblast activation. Targeting TEM1 may represent a novel therapeutic approach in reducing the morbidity of pathologic scars.