Fig. 1. GDF8 is a molecular transducer of musculoskeletal deficits that are obstinate to surgical reconstruction and rehabilitation following ligamentous injury.

(A) Participants with ACL injury underwent measures of knee extensor dynamometry, quadriceps biopsies, and periarticular bone mineral density at indicated time points pre- and post-reconstruction. (B) Knee extension peak isometric torque and (C) rate of torque development are reduced after ACL injury and do not recover. (D) Representative immunohistochemistry (IHC) image of muscle fiber cross-sectional area (CSA). Scale bars, 200 μm. (E) Quadriceps muscle fiber atrophy occurs progressively after ACL injury and does not recover. (F) Representative image from dual-energy x-ray absorptiometry (DXA). The red box indicates distal femoral metaphysis; the yellow box indicates proximal tibial metaphysis. Scale bar, 4 cm. Bone mineral density is decreased in the (G) proximal tibial metaphysis and (H) distal femoral metaphysis 6 months following ACLR. (I) GDF8/myostatin expression is elevated in the quadriceps muscle after ACL injury and remains elevated after ACL surgical reconstruction (ACLR). (J) Greater loss of quadriceps/knee extension strength, quadriceps size, and periarticular bone density at 4 to 6 months after reconstruction are correlated with quadriceps muscle GDF8 expression after ACL injury. Scatterplots can be seen in fig. S3. N = 23 (B to E and I), 21 (G and H). **P < 0.01, ***P < 0.005, and ****P < 0.001 versus healthy via mixed effects model and Dunnett’s correction for multiple comparisons. AU, arbitrary units; GDF8KO, GDF8 knockout; BMD, bone mineral density; RTD, rate of torque development.