Objective

Osteoarthritis (OA) pathogenesis involves the interaction of articular cartilage with surrounding tissues, which are innervated by tyrosine hydroxylase-positive (TH+) sympathetic nerve fibers suggesting a role of the sympathetic nervous system (SNS) during OA progression. We analyzed the effects of sympathectomy (Syx) in a murine OA model.

Methods

Peripheral Syx was generated by 6-hydroxydopamine (6-OHDA) injections in male C57BL/6 mice. OA was induced in wild-type (WT) and Syx mice by destabilization of the medial meniscus (DMM). TH+ fibers and splenic NE were analyzed to evaluate Syx efficiency. OA progression was examined by OARSI and synovitis scores and micro-CT. Expression of TH, α2A- and β2-adrenergic receptors (AR), and activity of osteoblasts (ALP) and osteoclasts (TRAP) was investigated by stainings.

Results

Syx resulted in synovial TH+ fiber elimination and splenic NE decrease. Cartilage degradation and synovitis after DMM were comparably progressive in both WT and Syx mice. Calcified cartilage (CC) and subchondral bone plate (SCBP) thickness and bone volume fraction (BV/TV) increased in Syx mice due to increased ALP and decreased TRAP activities compared to WT 8 weeks after DMMWT and Syx mice developed osteophytes and meniscal ossicles without any differences between the groups. AR numbers decreased in cartilage but increased in synovium and osteophyte regions after DMM in both WT and Syx mice.

Conclusion

Peripheral dampening of SNS activity aggravated OA-specific cartilage calcification and subchondral bone thickening but did not influence cartilage degradation and synovitis. Therefore, SNS might be an attractive target for the development of novel therapeutic strategies for pathologies of the subchondral bone.

中文翻译：

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交感神经切除术加重了小鼠骨关节炎进展过程中的软骨下骨变化，而不影响软骨退化或滑膜炎症

客观的

骨关节炎 (OA) 发病机制涉及关节软骨与周围组织的相互作用，这些组织由酪氨酸羟化酶阳性 (TH+) 交感神经纤维支配，表明交感神经系统 (SNS) 在 OA 进展过程中的作用。我们分析了交感神经切除术 (Syx) 在小鼠 OA 模型中的影响。

方法

外周 Syx 是通过在雄性 C57BL/6 小鼠中注射 6-羟基多巴胺 (6-OHDA) 产生的。通过内侧半月板（DMM）的不稳定在野生型（WT）和Syx小鼠中诱导OA。分析 TH+ 纤维和脾 NE 以评估 Syx 效率。通过 OARSI 和滑膜炎评分以及显微 CT 检查 OA 进展。通过染色研究 TH、α2A-和 β2-肾上腺素能受体 (AR) 的表达，以及成骨细胞 (ALP) 和破骨细胞 (TRAP) 的活性。

结果

Syx 导致滑膜 TH+ 纤维消除和脾脏 NE 减少。DMM 后的软骨退化和滑膜炎在 WT 和 Syx 小鼠中的进展程度相当。与 WT 相比，DMMWT 和 Syx 小鼠在没有出现骨赘和半月板小骨的情况下 8 周后，由于 ALP 增加和 TRAP 活性降低，Syx 小鼠的钙化软骨 (CC) 和软骨下骨板 (SCBP) 厚度和骨体积分数 (BV/TV) 增加组之间的任何差异。在 WT 和 Syx 小鼠中，在 DMM 后，软骨中的 AR 数量减少，但滑膜和骨赘区域的数量增加。

结论

SNS 活动的外周抑制加重了 OA 特异性软骨钙化和软骨下骨增厚，但不影响软骨退化和滑膜炎。因此，SNS 可能是开发新的软骨下骨病理治疗策略的有吸引力的目标。