Effect of Mesenchymal Stem Cell Exosomes on Osteoblast Activity in Osteoporotic Rat Models

Abstract

Osteoporosis is a condition marked by the deterioration of bone density due to disrupted bone remodeling, primarily driven by decreased osteoblast activity. Exosomes derived from Mesenchymal Stem Cells {MSCs} have the potential to stimulate bone regeneration; however, their precise effects on osteoblast activity remain ambiguous. This study aimed to assess the impact of MSC exosomes on osteoblast function, evaluated through osteoblast quantity, metaphyseal thickness, and osteogenic marker expression {Alkaline phosphatase/ALP, Collagen type I alpha 1/Col1a1, and Osteocalcin} in ovariectomy-induced osteoporotic rat models. Thirty female Wistar rats were randomly allocated into 5 groups: Sham, Osteoporosis {OVX/Ovariectomy + PBS}, High-Dose Exosomes {OVX + 8.5×10⁴ particles}, Low-Dose Exosomes {OVX + 8.5×10³ particles}, and Positive Control {OVX + Risedronate}. Following a 6-week post-ovariectomy period, interventions were administered intraperitoneally for 2 weeks. Serum ALP, Col1a1, and Osteocalcin were quantified via ELISA (Enzyme-Linked Immunosorbent Assay). The femoral metaphysis was examined histologically using H&E staining. Osteoporosis induction significantly decreased all parameters compared with the Sham group (p < 0.05). High-dose MSC exosome administration significantly increased metaphyseal thickness compared to the untreated osteoporosis group (p = 0.014) and restored osteoblast numbers (58.33 vs 34.00 cells/HPF (High Power Field); p < 0.05). Molecularly, high-dose exosome therapy significantly elevated the differentiation marker ALP (91.94 vs 69.90 U/L), matrix marker Col1a1 (15.27 vs 11.30 ng/mL), and mineralization marker Osteocalcin (4.38 vs 3.55 ng/mL), achieving levels comparable to healthy controls. These findings demonstrate that MSC exosomes effectively restore osteoblast activity and trabecular bone microarchitecture. Thus, MSC exosomes present a promising novel, cell-free, anabolic therapeutic strategy for osteoporosis management.

HIGHLIGHTS

• High-dose MSC exosome administration has been shown to significantly restore metaphyseal bone thickness and restore osteoblast cell populations in a rat model for postmenopausal osteoporosis.
• Exosome therapy effectively increased osteogenic markers, namely serum levels of Alkaline Phosphatase (ALP), Collagen type 1 (Col1a1), and Osteocalcin, indicating the reactivation of bone formation and matrix mineralization.
• This study demonstrated that the regenerative ability of MSC exosomes was statistically equivalent to that of the standard drug Risedronate, making it a potential new cell-free therapeutic candidate with an anabolic mechanism for the management of osteoporosis.

GRAPHICAL ABSTRACT