caused by overload or overuse修饰哪个？

The pathophysiology of this is disease is not completely understood. It used to be considered primarily a disease of hyaline cartilage with secondarily bone involvement, caused by overload or overuse, but the development of osteoarthritis has been found to be much more complicated.The role of synovitis and pro-infammatory mediators in the pathogenesis of OA is increasingly being appreciated [9, 10]. The role of synovial infammation is critical in producing the symptoms and structural progression of OA [11].It also correlates with symptom severity, rate of cartilage degeneration, and osteophyte development [12, 13]. A number of pathways and immune mediators are involved in the degeneration of articular cartilage, synovial immunopathogenesis, and in subchondral bone degeneration.The interaction of these proinfammatory cytokines, reactive oxygen species (ROS), nitric oxide, matrix degrading enzymes, and biomechanical stress are ultimately responsible for the progression of OA in synovial joints.Improved understanding of the mechanisms pro moting synovial infammation in OA will eventually lead to novel therapeutic targets for controlling symptoms and slowing structural destruction of the joints. The measurement of infammatory markers may also be useful in future as surrogate markers of disease activity or progression when evaluating effectiveness of an intervention [14].

骨性关节炎的病理生理学机制尚未明了。由于超负荷或过度使用，过去常认为骨性关节炎主要是透明软骨病，其次是骨受累，但现在发现骨性关节炎的发展要复杂得多。滑膜炎和促炎介质在骨性关节炎发病中的作用日益受到重视 [9，10]。滑膜炎症在 OA症状的产生和结构退变中起关键作用 [11]，与症状严重程度、软骨退变率和骨赘发展相关 [12，13]。许多通路和免疫介质参与关节软骨退变、滑膜免疫病理和软骨下骨退变。这些促炎细胞因子、活性氧（reactive oxygen species，ROS）、一氧化氮、基质降解酶和生物应力的相互作用最终导致了滑膜关节的骨性关节炎的进展。对骨性关节炎中促进滑膜炎症的机制的更深入了解，最终有助于发现用以控制症状和减缓结构破坏的治疗新靶点。在评估干预的有效性时，炎症标志物的测量也可能在未来作为疾病活动或进展的替代标志物[14]。

1.caused by overload or overuse是修饰a disease of hyaline cartilage ？还是 bone involvement？或者是primarily a disease of hyaline cartilage with secondarily bone involvement整个？为啥？

2.also有必要加吗？前面不是也是the symptoms and structural，现在是顺下来的，完全讲的一个东西