Table 2 Regulatory roles of the SNS in arthritis
Experimental model | Bone cell lineage | Key factors | Intervention | Actions and their mechanisms | Ref. |
|---|---|---|---|---|---|
In vitro: chondrocytes | ACs | NE | NE treatment (10−6 mol/L and 10−8 mol/L); IL-1β (0.5 ng/mL) to simulate inflammation | High NE concentrations inhibit IL-1β-induced IL-8 and MMP-13 expression, reverse GAG and type II collagen reduction, and reduce proliferation. Low NE concentrations induce apoptosis and promote proliferation. | |
In vitro: chondrocytes; in vivo: mouse OA | ACs | DA | In vitro: DA (25, 50, 100 μmol/L); IL-1β In vivo: IA injection of DA weekly for 12 weeks post-OA induction | DA inhibits IL-1β-induced NF-κB signaling and JAK2/STAT3 phosphorylation, exerting anti-inflammatory and anti-catabolic effects, protecting chondrocytes. | |
In vitro: chondrocytes | ACs | NE | NE and β-AR antagonist (0.1, 1.0, 10 μg/mL); IL-1β | β-AR signaling reduces MMPs expression and increases matrix protein synthesis by inhibiting JNK/ERK/NF-κB pathways. | |
In vivo: SD rats | ACs | NPY | No external intervention; observation at P1/P5/P10 time points during natural cartilage development | Nerve fibers gradually degrade during cartilage development, accompanied by increased SP and NPY release. | |
In vitro: chondrocytes; in vivo: mouse OA | ACs | NPY | In vitro: NPY (0–100 nmol/L); NPY2R antagonist (1 μmol/L); mTORC1 inhibitor rapamycin (50 nmol/L) In vivo: IA injection of NPY (10 μmol/L, 10 μL/injection, 1x/week × 8 weeks) or NPY2R antagonist (1 μmol/L) | NPY promotes chondrocyte hypertrophy and cartilage degradation via NPY2R-mediated activation of the mTORC1 signaling pathway. | |
In vitro: SFs | SFs | Leptin | Leptin (0.1–3 μmol/L); signaling pathway inhibitors | Leptin induces IL-6 expression in human SFs via the OBRl receptor signaling pathway. | |
In vitro: SFs | SFs | Leptin | Leptin (0.1–3 μmol/L); signaling pathway inhibitors | Leptin induces IL-8 expression in human SFs via the leptin receptor, IRS-1, PI3K, and Akt cascade and promotes NF-κB/p300 binding. | |
In vitro: chondrocytes | ACs | Leptin | Leptin (0, 10, 100, 200 ng/mL); mTOR inhibitor rapamycin; Ob-Rb overexpression | High Ob-Rb expression enhances leptin signaling sensitivity, activating the mTOR pathway, inhibiting autophagy, and inducing cell senescence. | |
In vivo: CIA mice, adjuvant rats; in vitro: immune cells | None | NE, NPY | In vivo: sympathectomy; NE treatment (10−6 mol/L and 10−8 mol/L) | SNS plays a pro-inflammatory role early by promoting Th1/Th17 responses, antibody production, and a late anti-inflammatory response through the appearance of Tr1+ cells and β2-AR-mediated inflammation inhibition. | |
In vitro: SFs | SFs | DA | DA treatment (10−9 to 10−5 mol/L) | DA inhibits IL-6 and IL-8 secretion via D1-like receptors. | |
In vivo: CIA mice In vitro: macrophages | OC | DA | In vivo: D1R antagonist: (0.005 mg/kg or 0.05 mg/kg), every other day; D1R agonist: i (0.2–2.0 mg/kg) | D1R antagonist ameliorates arthritis severity and inhibits osteoclast differentiation by suppressing D1R. | |
In vivo: CIA mice, Drd2−/−, Drd1−/− mice | None | DA | In vivo: D2R agonist (quinpirole, 0.3 mg/kg, IP, 2x/week × 3 weeks) | D2R agonist alleviates arthritis by downregulating Th17 cytokines and upregulating Treg cytokines. | |
In vitro: OB, OC | OB, OC | DA | D1-like receptor agonist (10−6 to 10−8 mol/L); D2-like receptor agonist (10−6 to 10−8 mol/L) | DA promotes bone formation via D2-like receptors in RA without affecting bone resorption. |
