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Updated: Jan 5, 2026
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Kinsenoside attenuates osteoarthritis by repolarizing macrophages through inactivating NF-κB/MAPK signaling and
Feng Zhou1, Jingtian Mei1, Xiuguo Han1
1Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People׳s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Abstract:
The objective was to investigate the effect of kinsenoside (Kin) treatments on macrophage polarity and evaluate the resulting protection of chondrocytes to attenuate osteoarthritis (OA) progression. RAW264.7 macrophages were polarized to M1/M2 subtypes then administered with different concentrations of Kin. The polarization transitions were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR), confocal observation and flow cytometry analysis. The mechanism of Kin repolarizing M1 macrophages was evaluated by Western blot. Further, macrophage conditioned medium (CM) and IL-1β were administered to chondrocytes. Micro-CT scanning and histological observations were conducted in vivo on anterior cruciate ligament transection (ACLT) mice with or without Kin treatment. We found that Kin repolarized M1 macrophages to the M2 phenotype. Mechanistically, Kin inhibited the phosphorylation of IκBα, which further reduced the downstream phosphorylation of P65 in nuclear factor-κB (NF-κB) signaling. Moreover, Kin inhibited mitogen-activated protein kinases (MAPK) signaling molecules p-JNK, p-ERK and p-P38. Additionally, Kin attenuated macrophage CM and IL-1β-induced chondrocyte damage. In vivo, Kin reduced the infiltration of M1 macrophages, promoted M2 macrophages in the synovium, inhibited subchondral bone destruction and reduced articular cartilage damage induced by ACLT. All the results indicated that Kin is an effective therapeutic candidate for OA treatment.
Insights
Kinsenoside (Kin) effectively shifts M1 macrophages to the M2 phenotype, offering chondrocyte protection and attenuating osteoarthritis progression by inhibiting key inflammatory pathways. This suggests Kin as a promising therapeutic for OA.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage breakdown and inflammation.
- Macrophage polarization plays a critical role in OA pathogenesis, with M1 macrophages promoting inflammation and M2 macrophages exhibiting anti-inflammatory and reparative functions.
Purpose of the Study:
- To investigate the therapeutic potential of kinsenoside (Kin) in modulating macrophage polarity.
- To evaluate the protective effects of Kin on chondrocytes and its ability to attenuate osteoarthritis progression.
Main Methods:
- RAW264.7 macrophages were polarized to M1/M2 subtypes and treated with Kin.
- Macrophage polarization was assessed using qRT-PCR, confocal microscopy, and flow cytometry.
- Western blotting was employed to elucidate Kin's mechanism of action.
- Chondrocyte damage was induced by macrophage conditioned medium (CM) and IL-1β.
- In vivo studies utilized anterior cruciate ligament transection (ACLT) mouse models with Micro-CT and histological analyses.
Main Results:
- Kin treatment successfully repolarized M1 macrophages to the M2 phenotype.
- Kin inhibited NF-κB signaling by reducing IκBα and P65 phosphorylation.
- Kin suppressed MAPK signaling pathways (JNK, ERK, P38).
- Kin attenuated IL-1β and CM-induced chondrocyte damage.
- In vivo, Kin reduced M1 macrophage infiltration, increased M2 macrophages, inhibited subchondral bone destruction, and lessened articular cartilage damage in ACLT mice.
Conclusions:
- Kinsenoside demonstrates significant immunomodulatory effects by repolarizing macrophages towards an anti-inflammatory M2 phenotype.
- Kin protects chondrocytes from inflammatory damage and mitigates OA progression through inhibition of NF-κB and MAPK signaling pathways.
- These findings highlight Kinsenoside as a potent therapeutic candidate for osteoarthritis treatment.
