Abstract
Inflammation is a common symptom in joint disorders such as rheumatoid arthritis, osteoarthritis (OA) and implant aseptic loosening (AL). The sympathetic nervous system is well known to play a critical role in regulating inflammatory conditions, and imbalanced sympathetic activity has been observed in rheumatoid arthritis. In AL it is not clear whether the sympathetic nervous system is altered. In this study we evaluated the systemic and local profile of neuroimmune molecules involved in the interplay between the sympathetic nervous system and the periprosthetic inflammation in hip AL. Our results showed that periprosthetic inflammation does not trigger a systemic response of the sympathetic nervous system, but is mirrored rather by the impairment of the sympathetic activity locally in the hip joint. Moreover, macrophages were identified as key players in the local regulation of inflammation by the sympathetic nervous system in a process that is implant debris-dependent and entails the reduction of both adrenergic and Neuropetide Y (NPY)-ergic activity. Additionally, our results showed a downregulation of semaphorin 3A (SEMA3A) that may be part of the mechanism sustaining the periprosthetic inflammation. Overall, the local sympathetic nervous system emerges as a putative target to mitigate the inflammatory response to debris release and extending the lifespan of orthopedic implants.
Highlights
Osteoarthritis (OA) is one of the most prevalent chronic joint diseases and a major contributor to functional disability and loss of autonomy in older adults[1]
In order to investigate the impact of periprosthetic inflammation on the systemic sympathetic nervous system activity, the serum levels of norepinephrine, epinephrine and neuropeptide Y (NPY) were measured in aseptic loosening (AL) patients, OA patients, and healthy donors
In this study we show that the periprosthetic inflammatory response is not decoded by the sympathetic nervous system at systemic levels, but is mirrored locally in the hip joint by the impairment of adrenergic and NPY-ergic activity in macrophages
Summary
Osteoarthritis (OA) is one of the most prevalent chronic joint diseases and a major contributor to functional disability and loss of autonomy in older adults[1]. Total joint replacements can fail, mostly due to periprosthetic inflammation featured by sustained chronic inflammatory response initiated by implant degradation products that shed and accumulate in the neighbor tissue[4]. This adverse tissue reaction is orchestrated by a large plethora of immune cells of which the macrophage lineage has been shown to be of major relevance[4,5]. We reported similar absence of sympathetic nerve fibers in periprosthetic tissues from AL patients while, again, in OA patients this does not occur[21] In this line of evidence, the sympathetic activity is affected by the intensity of inflammation in the joint.
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