Potential roles for the small leucine-rich proteoglycans biglycan and fibromodulin in ectopic ossification of tendon induced by exercise and in modulating rotarod performance

We present a detailed comparison of ectopic ossification (EO) found in tendons of biglycan (Bgn), fibromodulin (Fmod) single and double Bgn/Fmod-deficient (DKO) mice with aging. At 3 months, Fmod KO, Bgn KO and DKO displayed torn cruciate ligaments and EO in their quadriceps tendon, menisci and cruciate and patellar ligaments. The phenotype was the least severe in the Fmod KO, intermediate in the Bgn KO and the most severe in the DKO. This condition progressed with age in all three mouse strains and resulted in the development of large supernumerary sesmoid bones. To determine the role of exercise in the extent of EO, we subjected normal and DKO mice to a treadmill exercise 3 days a week for 4 weeks. In contrast to previous findings using more rigorous exercise regimes, the EO in moderately exercised DKO was decreased compared with unexercised DKO mice. Finally, DKO and Bgn KO mice tested using a rotarod showed a reduced ability to maintain their grip on a rotating cylinder compared with wild-type controls. In summary, we show (1) a detailed description of EO formed by Bgn, Fmod or combined depletion, (2) the role of exercise in modulating EO and (3) that Bgn and Fmod are critical in controlling motor function.