Table 1 The role of the JAK2/STAT3 signaling pathway in OA
From: Regulation and therapy, the role of JAK2/STAT3 signaling pathway in OA: a systematic review
Study type | Upstream regulator | Target cell/tissue | Effect on JAK2/STAT3 | Mechanism | Consequence | References |
|---|---|---|---|---|---|---|
In vitro study | HIF-1α | MLO-Y4 | Activation | RANKL↑ | Promoted osteocyte-mediated osteoclastic differentiation in vitro | [53] |
In vitro and vivo study | DA | C28/I2 cells DMM-induced OA C57BL/6 mice | Inhibition | iNOS↓, COX-2↓, MMP-1↓, MMP-3↓, MMP-13↓ COL-II↑, AGG↑ | Delayed articular cartilage degradation in OA Abrogated the degradation of cartilage matrix and reduced Osteoarthritis Research Society International scores | [34] |
In vitro and vivo study | TRIM59 | Primary human OA chondrocyte ACLT-induced OA SD rats | Inhibition | IL-1β↓, MMP-13↓, COL-II↑, AGG↑ | Maintained the balance of ECM and inhibited the production of proinflammatory cytokine and apoptosis. Enhanced cell viability. Alleviated IL-1β-driven cartilage matrix degradation | [35] |
In vitro and vivo study | INSR | Mice chondrocytes ACLT-induced OA C57BL/6 J mice | Inhibition | COL-II↑, GAG↑, p-JAK2↑, p-STAT3↑ ADAMTs-4↓, MMP-3↓, MMP-13↓ | Decreased the chondrocytes apoptosis and ameliorated the pathological symptoms of OA | [36] |
In vitro study | Inc RNA DANCR | Human chondrocytes | Inhibition | IL-6↓, IL-8↓ | Promoted inflammation, cell proliferation, and suppressed apoptosis | [41] |
In vitro and vivo study | DUSP19 | Rat chondrocytes ACLT-induced OA SD rats | Inhibition | p-JAK2/JAK↓, p-STAT3/STAT3↓, Bax↑, Caspase-3↑, Bcl-2↓, MMP-3↓, MMP-9↓, MMP-13↓ | Inhibited chondrocytes apoptosis and MMPs expression | [45] |
In vivo study | PTH (1–34) | Collagenase-induced OA C57BL/6 mice | Inhibition | COL-II↑,AGG↑,ADAMTS-4↓,MMP-13↓,Caspase-3↓,P53,Bax↓, P-JAK2, P-STAT3↓ | Ameliorated cartilage degeneration and subchondral bone deterioration | |
In vitro and vivo study | Leptin | Rat chondrocytes C28/I2 and T/C-28a2 cells Human FLS ACLT-induced OA SD rats | Inhibition | MMP-9↑, MMP-13↑, ROS↑, iNOS↑, Bax↑, Bcl-2↓, Belin-1↓, LC3↓ | Induced apoptosis. Regulated expression of Frizzled receptors in chondrocytes. Promoted expression of IL-6 and IL-8 | |
In vitro and vivo study | BCP | Mice chondrocytes MNX-induced OA C57BL/6 mice Human cartilage explants | Inhibition | IL-6↓, MMP-13, MMP-3, ADAMTS-4, ADAMTS-5 | BCP crystals and IL-6 form a positive feedback loop leading to OA | [40] |
In vitro study | CXCL16 | Human FLS | Activation | RANKL↑ | Upregulated RANKL expression | [64] |
In vitro study | Ghrelin | Human chondrocytes | Inhibition | MMP-3↓, ADAMTs-4↓, ADAMTS-5↓, COL-II↑, AGG↑ | Protected articular cartilage matrix destruction | [30] |
In vitro study | AGEs | Porcine chondrocyte | inhibition | MMP-3↓, ADAMTs-4↓, ADAMTS-5↓, COL-II↑, AGG↑ | Prevented AGE-mediated decrease of COL-II and AGG | [33] |
In vitro study | IL-22/IL-22R1 | Human FLS | Inhibition | inhibited JAK2/STAT3 p-STAT3↑, MMP-1↑, S1001A8/A9↑ | Amplified FLS activation | [61] |