Objective To observe the alleviating effect of transcutaneous auricular vagus nerve stimulation(taVNS) on articular cartilage and bone destruction in rats with collagen-induced arthritis(CIA)

and explore the cellular and molecular mechanisms of taVNS against rheumatoid arthritis(RA). Methods The male SD rats were randomly divided into normal control group(n=12)

model group(n=12)

and taVNS group(n=12). The CIA rat model was established by multi-point injection of emulsion prepared from type Ⅱ bovine collagen and Freund's incomplete adjuvant into the root of rat tail. The rats in the taVNS group were treated with taVNS at bilateral auricular conchae

30 min per time

once a day

for consecutive 28 d. The cartilage destruction of the ankle joint was observed by safranin O-fast green staining

the production of osteoclasts in the joint tissue by tartrate-resistant acid phosphatase(TRAP) staining

and the bone erosion by X-ray and Micro-CT imaging. The protein expression levels of matrix metalloproteinase(MMP)-1

MMP-3

MMP-13

receptor activator of nuclear factor-κB ligand(RANKL)

and osteoprotegerin(OPG) in the synovial tissues were detected by Western blot. Results Compared with the normal control group

the CIA rats presented with typical RA symptoms and elevated arthritis index(AI

P<0.05). After intervention with taVNS

the AI remarkably declined in comparison with that in the model group(P<0.05). Compared with the control group

the model group displayed loss of cartilage matrix in the ankle joint

thinned cartilage layer

obvious cartilage damage

and increased number of osteo-clasts in the joint(P<0.01); the imaging results showed bone loss and three-dimensional structural destruction of ankle joint and aggravated bone erosion(P<0.01); the expression levels of MMP-1

MMP-3 and MMP-13

and RANKL/OPG ratio were significantly elevated in the synovial tissue of ankle joint(P<0.01

P<0.05)

while the expression level of OPG was decreased(P<0.05). Compared with the model group

taVNS resulted in relatively intact cartilage layer of ankle joint

alleviated cartilage destruction

decreased number of osteoclasts(P<0.01)

improved bone erosion

loss

and three-dimensional structural destruction(P<0.01)

and diminished MMP-1

MMP-3

and MMP-13 expression and RANKL/OPG ratio in the synovial tissue of ankle joint(P<0.05

P<0.01)

while the expression level of OPG was increased(P<0.05). Conclusion taVNS effectively relieves bone and cartilage destruction in CIA rats

which might be related to its efficacy in reducing the production of osteoclasts in joint tissues and down-regulating the expression levels of MMP-1

MMP-3 and MMP-13

and RANKL/OPG ratio.