Faculty of Dentistry, McGill University, Montreal, Quebec, Canada; The Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada.
Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Osteoarthritis Cartilage. 2022 Jan;30(1):110-123. doi: 10.1016/j.joca.2021.06.014. Epub 2021 Sep 14.
To examine the effect of running exercise on behavioral measures of pain and intervertebral disc (IVD) inflammation in the SPARC-null mouse model.
Male and female 8-month old SPARC-null and age-matched control mice received a home cage running wheel or a control, fixed wheel for 6 months. Behavioral assays were performed to assess axial discomfort (grip test) and radiating leg pain (von Frey, acetone tests) and voluntary running was confirmed. Expression of inflammatory mediators (TNF-α, IL-1β, IL-2, IL-10, CCL5, CXCL1, CXCL5, RANKL, M-CSF, and VEGF) in IVDs was determined. Additional inflammatory (IL-1β, IL-1Ra, CXCR1, CXCR2) and macrophage phenotypic markers (ITGAM, CD80, CD86, CD206, Arg1) in IVDs were investigated by qPCR.
Voluntary running attenuated behavioral measures of pain in male and female SPARC-null mice. Increases in mediators including IL-1β, CXCL1 and CXCL5 were observed in SPARC-null compared to control IVDs. After 6 months of running, increases in M-CSF and VEGF were observed in male SPARC-null IVDs. In females, pro-inflammatory mediators, including CXCL1 and CXCL5 were downregulated by running in SPARC-null mice. qPCR analysis further confirmed the anti-inflammatory effect of running in female IVDs with increased IL-1Ra mRNA. Running induced upregulation of the macrophage marker ITGAM mRNA in males.
Voluntary running reversed behavioral signs of pain in male and female mice and reduced inflammatory mediators in females, but not males. Thus, the therapeutic mechanism of action may be sex-specific.
研究跑步运动对 SPARC 基因缺失小鼠模型的行为学疼痛指标和椎间盘（IVD）炎症的影响。
将 8 月龄雄性和雌性 SPARC 基因缺失小鼠及其同龄对照小鼠分别放入带有或不带有跑步轮的笼中饲养 6 个月。通过抓握测试评估轴向不适，通过 von Frey 纤维丝和丙酮测试评估放射状腿部疼痛，并确认小鼠的自发跑步行为。通过 qPCR 检测椎间盘内炎性介质（TNF-α、IL-1β、IL-2、IL-10、CCL5、CXCL1、CXCL5、RANKL、M-CSF 和 VEGF）的表达。进一步通过 qPCR 检测椎间盘内的炎性（IL-1β、IL-1Ra、CXCR1、CXCR2）和巨噬细胞表型标志物（ITGAM、CD80、CD86、CD206、Arg1）。
自发跑步减轻了雄性和雌性 SPARC 基因缺失小鼠的行为学疼痛指标。与对照组相比，SPARC 基因缺失小鼠的椎间盘内多种介质如 IL-1β、CXCL1 和 CXCL5 等表达增加。经过 6 个月的跑步后，雄性 SPARC 基因缺失小鼠的椎间盘内 M-CSF 和 VEGF 表达增加。在雌性小鼠中，跑步使 SPARC 基因缺失小鼠的椎间盘内促炎介质如 CXCL1 和 CXCL5 表达下调。qPCR 分析进一步证实了跑步对雌性椎间盘的抗炎作用，使 IL-1Ra mRNA 表达增加。跑步使雄性小鼠的巨噬细胞标志物 ITGAM mRNA 表达上调。
自发跑步减轻了雄性和雌性小鼠的行为学疼痛迹象，并减少了雌性小鼠的炎性介质，但对雄性小鼠没有影响。因此，其治疗作用机制可能具有性别特异性。
