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Inhibition of osteoclast activity by mesenchymal stem cell-derived exosomes in an ovariectomy-induced osteoporosis rat model

biochemistry
cell-biology
internal-medicine
rheumatology
translational-medicine

Abstract

Background: Postmenopausal osteoporosis, caused by estrogen deficiency, is characterized by excessive osteoclastic activity (bone resorption). Current standard therapies, such as bisphosphonates (Risedronate), have limitations due to severe side effects and low efficacy. Exosomes derived from mesenchymal stem cells (MSC-Exo) show outstanding therapeutic potential as anti-resorption agents. This study aimed to prove the effect of MSC-Exo inhibition on osteoclastic activity in an oophorectomy-induced osteoporosis (OVX) mouse model.

Methods: This study used an experimental design of a pre-test and post-test control group. A total of 25 Wistar mice were randomly divided into five groups (n=5): (1) Sham Control, (2) Osteoporosis (OVX + placebo), (3) OVX + Exosome dose 8.5x10⁴, (4) OVX + Exosome dose 8.5x10³, and (5) OVX + Risedronate. The osteoporosis model was induced through bilateral oophorectomy and left for 6 weeks. A treatment intervention was given for two weeks. The primary parameter is the osteoclast/osteocyte ratio, which is histopathologically analyzed (haematoxylin-eosin, H&E staining) in the metaphysis of the femur and calculated in a double-blind manner. The secondary parameter was serum C-terminal telopeptide of type I collagen (CTX) levels measured by ELISA before and after therapy. Non-parametric histopathological data were analyzed using Kruskal-Wallis and Mann-Whitney U, while CTX data were analyzed using one-way ANOVA and paired t-tests. P means if it is less than 0.05.

Results: Histopathological analysis showed a statistically significant difference in the ratio of osteoclasts/osteocytes among the five groups (p=0.025). The Mann-Whitney U assay confirmed that both exosome doses (8.5x10³ and 8.5x10⁴) significantly suppressed the ratio compared to the osteoporosis group (p=0.009 and p=0.047). The exosome group (8.5x10³) also had a significantly lower ratio (stronger inhibition) than the risedronate group (p=0.009). The paired T-test successfully confirmed the progression of the disease in the osteoporosis group, which showed a significant increase in CTX levels (p=0.040). MSC-Exo and risedronate successfully prevented the increase in CTX.

Conclusions: Exosomes derived from mesenchymal stem cells effectively inhibited osteoclastic activity in the mouse model of OVX. The histological anti-resorption effect of an exosome dose of 8.5x10³ was shown to be statistically superior to standard therapy, Risedronate. MSC-Exo and risedronate successfully prevented increased serum CTX levels.

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