Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviate Histological Damage and Modulate ADAM12 Gene Expression in the Type 2 Diabetic Rat Model of Achilles Tendinopathy

Diabetic Achilles tendinopathy (AT) is a degenerative disease resulting from changes in tendon tissue homeostasis caused by type 2 diabetes mellitus. The cure of diabetic AT is difficult to achieve due to the limited regeneration capacity of the tendon. Therefore, a new approach to effectively improve AT healing is needed for further investigation. Previous research has investigated the effect of exosomes from bone marrow-derived mesenchymal stem cells (BM-MSC-Exos) in tendon pathological conditions. Nevertheless, their influence on a diabetic rat model of AT remains unexplored. This study aims to determine the effect of injection of BM-MSC-Exos on diabetic rat model of AT based on histology analysis and ADAM12 gene expression. A total of 12 male white Sprague Dawley rats were grouped into two groups consisting of the tendinopathy control group and the exosome group. Postmortem Achilles tendon histology analysis on day 21 was carried out using the semiquantitative Bonar score method, quantitative histomorphometry of ground substance, and histomorphometry of collagen area using hematoxylin-eosin, alcian blue, and Masson's trichrome staining. Changes in ADAM12 gene expression were examined quantitatively using qRT-PCR. The administration of BM-MSC-Exos in a diabetic Achilles tendinopathy rat model significantly improved tendon histology repair, as evidenced by a marked decrease in the Bonar score. Histomorphometric analysis of the ground substance area showed a significant decrease, indicating the inhibition of osteo-chondrogenic differentiation in the Achilles tendon. Although collagen area histomorphometry displayed an increasing trend, no significant difference was observed on day 21. No significant difference in relative ADAM12 mRNA expression was found between the control and treatment groups, despite an increasing trend observed in the exosome-injected group. The administration of BM-MSC-Exos was proven to have the potential to trigger improvement in diabetic Achilles tendinopathy on day 21.