目的:近年来,对artemin/GFRα3信号传导的认识有了显著的进展,现在有越来越多的证据表明artemin在疼痛信号传导中起着重要的作用,包括来自关节和骨骼的,与OA有关。
方法:本研究使用了163只SpragueDawley大鼠。我们使用了单碘乙酸(MIA)诱导的OA动物模型,结合电生理学,行为测试,蛋白质印迹分析,逆行追踪和免疫组织化学,确定artemin/GFRα3信号传导在OA疼痛发病机制中的作用。
结果:我们发现:1)GFRα3在相当大比例的膝关节传入神经元中表达;2)外源性Artemin使幼稚大鼠的膝关节传入神经元敏感;3)Artemin在关节的关节组织中表达,但不是周围的骨头,在MIA诱导的OA早期;4)当病理涉及软骨下骨时,在MIA诱导的OA中,artemin在骨骼中的表达增加;5)当膝关节组织炎症和软骨下骨损伤时,在疾病晚期,Artemin的隔离逆转了MIA诱导的膝关节和骨传入神经元的敏感性。
结论:我们的研究结果表明,artemin/GFRα3信号传导在OA疼痛的发病机制中起作用,通过对膝关节和骨传入神经元的影响,并提示Artemin/GFRα3信号传导的靶向操作可能为OA疼痛的管理提供治疗益处。
方法:数据可应相应作者的要求提供。
There have been significant developments in understanding
artemin/GFRα3 signaling in recent years, and there is now accumulating evidence that
artemin has important roles to play in pain signaling, including that derived from joint and bone, and that associated with osteorthritis (OA).
A total of 163 Sprague-Dawley rats were used in this study. We used an animal model of mono-iodoacetate (MIA)-induced OA, in combination with electrophysiology, behavioral testing, Western blot analysis, and retrograde tracing and immunohistochemistry, to identify roles for artemin/GFRα3 signaling in the pathogenesis of OA pain.
We have found that: 1) GFRα3 is expressed in a substantial proportion of knee joint afferent neurons; 2) exogenous artemin sensitizes knee joint afferent neurons in naïve rats; 3)
artemin is expressed in articular tissues of the joint, but not surrounding bone, early in MIA-induced OA; 4)
artemin expression increases in bone later in MIA-induced OA when pathology involves subchondral bone; and 5) sequestration of artemin reverses MIA-induced sensitization of both knee joint and bone afferent neurons late in disease when there is inflammation of knee joint tissues and damage to the subchondral bone.
Our findings show that
artemin/GFRα3 signaling has a role to play in the pathogenesis of OA pain, through effects on both knee joint and bone afferent neurons, and suggest that targeted manipulation of artemin/GFRα3 signaling may provide therapeutic benefit for the management of OA pain.
Data are available on request of the corresponding author.