Recent studies have demonstrated that the small leucine-rich proteoglycans (SLRPs) biglycan and decorin impact tendon development, aging and healing in mature mice. However, despite the increased risk of tendon injury in the elderly, the role of SLRPs in tendon repair has not been investigated in aged animals. Therefore, our objective was to elucidate the influences of bigylcan and decorin on tendon healing in aged mice to relate our findings to previous work in mature mice. Since the processes of aging and healing are known to interact, our hypothesis was that aging mediates the role of biglycan and decorin on tendon healing. Patellar tendons from wild-type, biglycan-null and decorin-null mice were injured at 270 days using an established model. At 3 and 6 weeks post-surgery, structural, mechanical and biochemical analyses were performed and compared to uninjured controls. Early stage healing was inferior in biglycan-null and decorin-null mice as compared to wild type. However, tendons of all genotypes failed to exhibit improved mechanical properties between 3 and 6 weeks post-injury. In contrast, in a previous investigation of tendon healing in mature (i.e., 120 day-old) mice, only biglycan-null mice were deficient in early stage healing while decorin-null mice were deficient in late-stage healing. These results confirm that the impact of SLRPs on tendon healing is mediated by age and could inform future age-specific therapies for enhancing tendon healing.

Defining the constituent regulatory molecules in tendon is critical to understanding the process of tendon repair and instructive to the development of novel treatment modalities. The purpose of this study is to define the structural, expressional, and mechanical changes in the tendon injury response, and elucidate the roles of two class I small leucine-rich proteoglycans (SLRPs). We utilized biglycan-null, decorin-null and wild type mice with an established patellar tendon injury model. Mechanical testing demonstrated functional changes associated with injury and the incomplete recapitulation of mechanical properties after 6 weeks. In addition, SLRP deficiency influenced the mechanical properties with a marked lack of improvement between 3 and 6 weeks in decorin-null tendons. Morphological analyses of the injury response and role of SLRPs demonstrated alterations in cell density and shape as well as collagen alignment and fibril structure resulting from injury. SLRP gene expression was studied using RT-qPCR with alterations in expression associated with the injured tendons. Our results show that in the absence of biglycan initial healing may be impaired while in the absence of decorin later healing is clearly diminished. This suggests that biglycan and decorin may have sequential roles in the tendon response to injury.