Dimethyl Oxalylglycine Activates Tendon‐Derived Stem Cells to Promote Regeneration of Achilles Tendon Rupture in Rats via HIF‐1α

Abstract

Tendon-derived stem cells (TDSCs) are stem cells found in tendons that may become ideal seed cells for tendon repair. This study aims to investigate whether dimethyl oxalylglycine (DMOG) treatment could effectively improve the regeneration ability of TDSCs to repair Achilles tendon injury. Stem cells of rat Achilles tendon are isolated and treated with DMOG or Lificiguat (YC-1). The treated TDSCs are transplanted into rats with Achilles tendon injury. A batch of animals is sacrificed every week for biomechanical and historical analyses. The recovery of Achilles tendon is tested by biomechanics and histology. DMOG could activate TDSCs in vitro and improve their differentiation ability by regulating the expression levels of hypoxia-inducible factor-1𝜶 (HIF-1𝜶) and early growth response 1 (EGR1). As an inhibitor of HIF-1𝜶, YC-1 could weaken the effect of DMOG. TDSCs pre-treated with either DMOG or YC-1 are transplanted into rats with Achilles tendon injury, and DMOG pre-treatment could effectively improve the regeneration of Achilles tendon. In summary, DMOG improves TDSC differentiation ability, and transplanting TDSCs pre-treated with DMOG into rats with Achilles tendon injury can effectively improve tendon regeneration, which may serve as a novel approach for the treatment of Achilles tendon injury.

Effect of Dimethyloxalylglycine on Stem Cells Osteogenic Differentiation and Bone Tissue Regeneration—A Systematic Review

“…DMOG treatment has been shown to enhance the expression of angiogenic markers in stem cells [32,[42][43][44][45][46]69] and promote proliferation, migration, and tube formation in HUVECs [59,[61][62][63]67], thus effectively promoting angiogenesis. Additionally, DMOG enhances the angiogenic capacity of muscle-derived stem cells (MDSPCs) [49] and dental pulp cells (DPCs) [91,92].…”

“…Dimethyloxalylglycine (DMOG) is a pro-angiogenic small molecule drug with a chemical formula of C 6 H 9 NO 5 . DMOG is de-esterified in cells to form N-oxalylglycine (NOG), which inhibits the biological activity of PHD in a normal oxygen concentration environment and stabilizes the expression level of HIF-1α in cells under normoxia [42][43][44][45][46][47][48][49][50][51]. Its simple biochemical composition makes DMOG more stable and cost-effective, avoiding side effects like cells aging and reactive oxygen species (ROS) generation caused by cells cultured in a truly hypoxic environment.…”