Leucine rich repeat containing 32 accelerates tenogenic differentiation of tendon-derived stem cells and promotes Achilles tendon repair in rats

Abstract

Although many surgical or non-operative therapies have been developed to treat Achilles tendon injuries, the prognosis of which is often unsatisfactory. Recently, biologic approaches using multipotent stem cells like tendon-derived stem cells (TDSCs) pose a possible treatment option. To evaluate whether the Leucine rich repeat containing 32 (Lrrc32) affects the tenogenic differentiation of TDSCs and thus promotes Achilles tendon healing. TDSCs were infected with the recombinant Lrrc32-overexpressing lentivirus (LV-Lrrc32) and then locally injected into the injured site of rat. Four weeks after surgery, the Achilles tendon tissue (~0.5 cm) around the injured area was harvested for analysis. Pathological results showed that Lrrc32-overexpressing TDSCs significantly improved the morphological changes of the injured tendons. Specifically, the increased collagen-I expression and hydroxyproline content in extracellular matrix, and more orderly arrangement of the regenerated collagen fibers were observed in the Lrrc32 overexpression group.Moreover, 4 weeks after injection of Lrrc32-overexpressing TDSCs, the expression of tenocyte-related genes such as tenomodulin (Tnmd), scleraxis (Scx) and decorin (Dcn) were upregulated in the area of the healing tendon. These findings indicated that Lrrc32 promoted the tenogenic differentiation of TDSCs in vivo. Additionally, Lrrc32 overexpression also increased the expression of TGF-β1 and p-SMAD2/3, suggesting that the beneficial effects of Lrrc32 on tendon repair might be associated with the expression of TGF-β1 and p-SMAD2/3. Our findings collectively revealed that Lrrc32-overexpressed TDSCs promoted tendon healing more effectively than TDSCs alone.

The Functions and Mechanisms of Tendon Stem/Progenitor Cells in Tendon Healing

“…In addition to this, the combination of TSPCs with genes and proteins for the therapeutic treatment of tendon injury is also a focus of future investigation. Kang et al [ 138 ] established that TDSCs were infected with recombinant Lrrc32 overexpressing lentivirus (LV-Lrrc32) and then locally injected into the injury site of rats, and the results showed that Lrrc32 promoted the tendon differentiation of TDSCs in vivo and facilitated the healing of tendons in rats. In conclusion, TSPCs deserve further investigation as a potential cell therapy, both in terms of the factors that induce its multidirectional differentiation and the mechanisms by which it promotes tendon healing.…”