ISSLS Prize in Basic science 2019: Physical activity attenuates fibrotic alterations to the multifidus muscle associated with intervertebral disc degeneration

Purpose: Chronic low back pain causes structural remodelling and inflammation in the multifidus muscle. Collagen expression is increased in the multifidus of humans with lumbar disc degeneration. However, the extent and mechanisms underlying the increased fibrotic activity in the multifidus are unknown. Physical activity reduces local inflammation that precedes multifidus fibrosis during intervertebral disc degeneration (IDD), but its effect on amelioration of fibrosis is unknown. This study aimed to assess the development of fibrosis and its underlying genetic network during IDD and the impact of physical activity. Methods: Wild-type and SPARC-null mice were either sedentary or housed with a running wheel, to allow voluntary physical activity. At 12 months of age, IDD was assessed with MRI, and multifidus muscle samples were harvested from L2 to L6. In SPARC-null mice, the L1/2 and L3/4 discs had low and high levels of IDD, respectively. Thus, multifidus samples from L2 and L4 were allocated to low- and high-IDD groups compared to assess the effects of IDD and physical activity on connective tissue and fibrotic genes. Results: High IDD was associated with greater connective tissue thickness and dysregulation of collagen-III, fibronectin, CTGF, substance P, TIMP1 and TIMP2 in the multifidus muscle. Physical activity attenuated the IDD-dependent increased connective tissue thickness and reduced the expression of collagen-I, fibronectin, CTGF, substance P, MMP2 and TIMP2 in SPARC-null animals and wild-type mice. Collagen-III and TIMP1 were only reduced in wild-type animals. Conclusions: These data reveal the fibrotic networks that promote fibrosis in the multifidus muscle during chronic IDD. Furthermore, physical activity is shown to reduce fibrosis and regulate the fibrotic gene network. Graphical abstract: These slides can be retrieved under Electronic Supplementary Material.[Figure not available: see fulltext.].