Collagen XII deficiency induces myogene expression in subcutaneous adipose tissues

Collagen XII is highly expressed in skeletal tissues, and mutations in collagen XII cause myopathic Ehlers-Danlos syndrome, manifesting as early onset myopathy and joint disorder. Besides skeletal tissues and muscles, collagen XII has been detected in blood and matrix vesicles, and its expression in correlation with LDL is increased in patients with obesity. However, the roles of collagen XII in fat metabolism have not been elucidated. In this study, we aimed to explore the potential role of collagen XII in fat tissue using a Col12a1 null mouse model. Collagen XII deficiency reduced the volume of subcutaneous (ScAT), visceral (VAT), and brown adipose tissue (BAT). Adipocytes were smaller in Col12a1 null ScAT and VAT but not in BAT compared with those in wild-type controls. Real-time PCR analysis revealed that Col12a1 mRNA was expressed in VAT and ScAT. Microarray analysis of ScAT from Col12a1 null mice revealed 1243 genes with upregulated expression, 167 of which were implicated in cytoskeletal muscle structure and 153 of which were associated with muscle development. Among these genes, myostatin positive cells were clearly detected in Col12a1 null but not in wild-type ScAT, as revealed by immunohistochemistry. These results suggest that collagen XII is involved in ScAT homeostasis, and impairment of its expression may contribute to the development of myopathy by inducing ectopic activation of muscle-related genes and emergence of myostatin-positive cells in adipose tissue.