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Updated: Jun 28, 2025
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
BMSC-Derived Exosomes Attenuate Rat Osteoarthritis by Regulating Macrophage Polarization through PINK1/Parkin
Beibei Li1, Enpu Shen2, Zhiwen Wu1
1Department of Orthopaedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Abstract:
ObjectiveExosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) may modulate the M1/M2 polarization of macrophages during osteoarthritis (OA). However, the underlying mechanisms of BMSC-Exos in this process still need to be elucidated. In this study, we explored the role of BMSC-Exos in the polarization of macrophages in vitro and the OA rats in vivo.MethodsThe effects of BMSC-Exos on RAW264.7 cells were determined, including the production of reactive oxygen species (ROS) and the protein expression of Akt, PINK1, and Parkin. We prepared an OA model by resecting the anterior cruciate ligament and medial meniscus of Sprague-Dawley (SD) rats. Hematoxylin-eosin (H&E) and safranin O-fast green staining, immunohistochemistry and immunofluorescence analyses, and the examination of interleukin 6 (IL-6), interleukin 1β (IL-1β), tumor necrosis factor alpha (TNF-α), and interleukin 10 (IL-10) were performed to assess changes in cartilage and synovium.ResultsBMSC-Exos inhibited mitochondrial membrane damage, ROS production, and the protein expression of PINK1 and Parkin. Akt phosphorylation was downregulated under lipopolysaccharide (LPS) induction but significantly recovered after treatment with BMSC-Exos. BMSC-Exos alleviated cartilage damage, inhibited M1 polarization, and promoted M2 polarization in the synovium in OA rats. The expression of PINK1 and Parkin in the synovium and the levels of IL-6, IL-1β, and TNF-α in the serum decreased, but the level of IL-10 increased when BMSC-Exos were used in OA rats.ConclusionBMSC-Exos ameliorate OA development by regulating synovial macrophage polarization, and one of the underlying mechanisms may be through inhibiting PINK1/Parkin signaling.
Insights
Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) alleviate osteoarthritis by shifting synovial macrophage polarization. This mechanism involves inhibiting the PINK1/Parkin signaling pathway, offering a novel therapeutic strategy for OA.
Area of Science:
- Stem cell biology
- Immunology
- Orthopedics
Background:
- Osteoarthritis (OA) is characterized by chronic inflammation and cartilage degradation.
- Macrophage polarization, particularly the shift towards M1 pro-inflammatory phenotypes, plays a critical role in OA pathogenesis.
- Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have shown therapeutic potential, but their precise mechanisms in OA, especially regarding macrophage polarization, remain unclear.
Purpose of the Study:
- To investigate the role of BMSC-Exos in modulating macrophage polarization in osteoarthritis.
- To elucidate the underlying molecular mechanisms by which BMSC-Exos exert their effects on macrophages and OA progression.
Main Methods:
- Exosomes were isolated from bone marrow mesenchymal stem cells (BMSC-Exos).
- The effects of BMSC-Exos on RAW264.7 macrophage cell line were assessed, measuring reactive oxygen species (ROS) and key protein expression (Akt, PINK1, Parkin).
- An osteoarthritis rat model was established, and histological analyses (H&E, safranin O-fast green), immunohistochemistry, immunofluorescence, and serum cytokine level measurements (IL-6, IL-1β, TNF-α, IL-10) were performed.
Main Results:
- BMSC-Exos treatment reduced mitochondrial damage, ROS production, and PINK1/Parkin expression in vitro.
- Akt phosphorylation was restored by BMSC-Exos under inflammatory conditions.
- In OA rats, BMSC-Exos attenuated cartilage damage, inhibited M1 macrophage polarization, and promoted M2 polarization in the synovium.
- Synovial PINK1/Parkin expression and serum pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) were decreased, while anti-inflammatory IL-10 increased.
Conclusions:
- BMSC-Exos effectively ameliorate osteoarthritis development by regulating synovial macrophage polarization.
- Inhibition of the PINK1/Parkin signaling pathway is identified as a key mechanism underlying the therapeutic effects of BMSC-Exos in OA.
