Table 2 Therapeutic approaches to regulate JAK2/STAT3 in OA

MicroRNAs

MiR-375 inhibition

activation

ADAMTS-5↓, MMP-13↓, COL-II↑, AGG↑, p-JAK2/JAK2↑, p-STAT3/STAT3↑, Bcl-2/Bax↑

Improved the ability of chondrocytes to antagonize oxidative stress and maintain ECM homeostasis

[28, 67]

MiR-149-5p

Inhibition

AGT↓, ANGII, AT1R

Regulated and combined AGT, promoted the inflammatory responses induced by IL-6

[39]

MiR-216a-5p

Inhibition

Bax↓, Caspase-3↓, Bcl-2↑

Promoted the proliferation and migrations well as inhibited apoptosis in chondrocytes

[29]

MiR-224-5p

Inhibition

MMP-9↓, MMP-13↓, COL-II↑, AGG↑, Caspase-3↓, Circ_PDE1C↓

Inhibited chondrocytes apoptosis and ECM degradation. Targeted CCL2 and accelerated cartilage degradation

[44]

Traditional Chinese medicine

Danshen

activation

P-JAK2, p-STAT3↓, GSH, SOD, CAT↑, Bcl-2↑, Bax, caspase3, PARP↓

Attenuated cartilage injuries by activating JAK2/STAT3 pathway

[71]

Diosgenin

activation

P-JAK2, p-STAT3, SDH, COX, SOD↑, Bax↓

Protected OA cartilage cells by activating the JAK2/STAT3 pathway, which effectively reduces mitochondrial oxidative stress damage and apoptosis in OA cells during the pathological process

[73]

curcumin

activation

P-JAK2, p-STAT3,

Increased the mitochondrial resistance to oxidative stress in chondrocytes, significantly slows down the degeneration of articular cartilage, and reduces the level of OA progression

[75]

Resveratrol

Inhibition

JAK2, STAT3, SOCS3, MMP-13↓

No significant leptin resistance existed in articular cartilage of obesity-related OA and the inhibitory effect of RES on obesity-related OA via alleviating JAK2/STAT3 signaling pathway

[77]

Inhibitors

AG490

Inhibition

JAK2↓

Inhibited JAK2/STAT3 activation and apoptosis in chondrocytes induced by IL-1β

[62, 79]

WP1066

Inhibition

JAK2, STAT3↓

Downregulated the expression of JAK2/STAT3 to suppress the chondrocytic inflammation responses induced by IL-6

[39]

Tofacitinibis

Inhibition

JAK, STAT3↓

Moderated chondrogenic hypertrophy in human chondrocyte lines via downregulation of JAK/STAT3

[68]

Pranlukast

Inhibition

JAK2, STAT1↓

Reversed the enhancement levels of pro-inflammatory cytokines to prevent the progression of OA

[81]

STA21

Inhibition

STAT3↓

Blocked STAT3 dimerization and DNA binding to alleviate joint pain and cartilage damage

[82]

Stattic

Inhibition

STAT3↓

Reduced the severity of OA cartilage lesions and decreased the size of osteophytes. Stattic had no significant effect on the synovium or the subchondral bone

[55]