Vitamin D status associates with skeletal muscle loss after anterior cruciate ligament reconstruction.
BACKGROUND. Although 25-hydroxyvitamin D (25(OH)D) concentrations =30ng/mL are known to reduce injury risk and boost strength, the influence on anterior cruciate ligament reconstruction (ACLR) outcomes remains unexamined. This study aimed to define the vitamin D signaling response to ACLR, assess the relationship between vitamin D status and muscle fiber cross-sectional area (CSA) and bone density outcomes, and discover vitamin D receptor (VDR) targets post-ACLR. METHODS. 21 young, healthy, physically active participants with recent ACL tears were enrolled (62% female; 17.8 ± 3.2 yr, BMI: 26.0 ± 3.5 kg/m2). Data were collected through blood samples, vastus lateralis biopsies, DXA bone density measurements, and isokinetic dynamometer measures at baseline, 1 week, 4 months, and 6 months post-ACLR. The biopsies facilitated CSA, western blot, RNA-seq, and VDR ChIP-seq analyses. RESULTS. ACLR surgery led to decreased circulating bioactive vitamin D and increased VDR and activating enzyme expression in skeletal muscle one week post-operation. Participants with <30 ng/mL 25(OH)D levels (n=13) displayed more significant quadriceps fiber CSA loss one week and 4 months post-ACLR than those with =30 ng/mL (n=8; p<0.01 for post-hoc comparisons; p=0.041 for time x vitamin D status interaction). RNA-seq and ChIP-seq data integration revealed genes associated with energy metabolism and skeletal muscle recovery, potentially mediating the impact of vitamin D status on ACLR recovery. No difference in bone mineral density (BMD) losses between groups was observed. Overall design: The purpose of this experiment was to identify potential target of the vitamin D receptor in human skeletal muscle (quadriceps) one week after anterior cruciate ligament recontruction (ACLR). Skeletal muscle samples from several participants were combined for 1 week post-ACLR quadriceps samples . This approach was necessary to provide the requisite 150m, and only data from this one combined sample is included here. Participants were 16-30 years of age, healthy, and included males anf females.