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Paeoniflorin elevates the expression of SOCS3 in macrophages to prevent MIA-induced osteoarthritis in mice
Changlin Sun1, Xiqin Bian1, Xiuting Qi1
1Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Abstract:
Osteoarthritis (OA) is a degenerative joint disease that occurs frequently in middle-aged and elderly individuals, limiting joint function and causing disability with severe pain. However, available treatment options for inhibiting inflammation, preventing cartilage degradation, and relieving pain remain limited. Paeoniflorin, a monoterpene glycoside isolated from the Chinese medicine Paeonia lactiflora exhibits anti-inflammatory and immunomodulatory effects. In the present study, we investigated the efficacy and possible mechanisms of paeoniflorin in attenuating pain, inflammation, and cartilage degradation in a mouse model of OA. The analgesic effect of paeoniflorin was assessed by measuring mechanical allodynia with von Frey hairs. H&E staining was used to evaluate the structural integrity and inflammation of joint tissues. RAW264.7 cells were used to investigate the effects of paeoniflorin on related signaling pathways and on lipopolysaccharide (LPS)-induced inflammation by Western blotting. Paeoniflorin relieved mechanical allodynia and reduced cartilage degeneration in vivo. Moreover, paeoniflorin upregulated Gas6 expression, activated the Axl receptor, upregulated suppressor of cytokine signaling 3 (SOCS3) expression, inhibited MMP-9 expression, and decreased p38 phosphorylation in the joints. Cell experiments revealed that paeoniflorin regulated the Gas6-TAM pathway via the ERK signaling pathway and decreased MMP-9 expression and M1 polarization. Collectively, paeoniflorin may inhibit joint inflammation and relieve pain by upregulating the Gas6-TAM pathway and promoting macrophage M2 polarization, suggesting that it may serve as a potential therapeutic agent for osteoarthritis.
Insights
Paeoniflorin, derived from Chinese medicine, effectively reduces osteoarthritis pain and cartilage damage in mice. It works by modulating the Gas6-TAM pathway, promoting anti-inflammatory responses, and potentially offering a new therapeutic option for osteoarthritis.
Area of Science:
- Pharmacology
- Immunology
- Biochemistry
Background:
- Osteoarthritis (OA) is a prevalent degenerative joint disease causing pain and disability.
- Current treatments for OA inflammation, cartilage degradation, and pain are limited.
- Paeoniflorin, from Paeonia lactiflora, has known anti-inflammatory and immunomodulatory properties.
Purpose of the Study:
- To investigate paeoniflorin's efficacy in alleviating pain, inflammation, and cartilage degradation in a mouse OA model.
- To elucidate the underlying molecular mechanisms of paeoniflorin's therapeutic effects.
Main Methods:
- OA mouse model induced and treated with paeoniflorin.
- Assessment of mechanical allodynia using von Frey hairs.
- Histological analysis (H&E staining) of joint tissues.
- In vitro studies using RAW264.7 cells and Western blotting to analyze signaling pathways (Gas6-TAM, ERK) and inflammatory markers (MMP-9, M1/M2 polarization).
Main Results:
- Paeoniflorin significantly relieved mechanical allodynia and reduced cartilage degeneration in vivo.
- It upregulated Gas6 and activated the Axl receptor, increased SOCS3, inhibited MMP-9, and decreased p38 phosphorylation in joints.
- In vitro, paeoniflorin regulated the Gas6-TAM pathway via ERK, reduced MMP-9 expression, and inhibited M1 polarization, promoting M2 polarization.
Conclusions:
- Paeoniflorin demonstrates significant therapeutic potential for osteoarthritis.
- It alleviates pain and joint inflammation by upregulating the Gas6-TAM pathway and promoting M2 macrophage polarization.
- Paeoniflorin may serve as a novel therapeutic agent for managing osteoarthritis symptoms.