About this Research Topic
Rheumatic diseases, such as rheumatoid arthritis (RA), osteoarthritis (OA) or spondyloarthritis, all result in erosive damage in joint tissues as cartilage and bone and are accompanied by synovial inflammation in varying severity. Some rheumatic disorders, especially RA, are considered as systemic inflammatory diseases generally affecting the joints symmetrically, while others as OA mostly manifest locally in single joints. However, it has become clear over the past two decades that in all rheumatic diseases a significant crosstalk between cells of both innate and adaptive immunes system and bone cells exists, now termed “osteoimmunology”, that strongly influence bone homeostasis and pathology. While evolutionarily adaptive for normal processes such as fracture healing, many immunocyte-derived and -influencing mediators (e.g. TNFα, IL-1, IL-6, anti-citrullinated protein antibodies, RANKL) exert potent catabolic effects, driving cartilage and bone loss adjacent to the inflamed synovium of patients with rheumatic disorders and contributing to functional disability. Understanding this crosstalk has been area of research with implications for better control of disease through development of targeted clinical therapies.
It has become clear that there is another contributor, moderator, and sometimes conductor of this intricate localized crosstalk, namely the peripheral nervous system with its sensory and autonomic branches, and by extension, neurotransmitters that make up the neural vocabulary. The bidirectional interaction and integration of the nervous and immune systems to affect immunologic homeostasis is well established and have been partly mapped into distinct circuits and reflexes, particularly those involving the vagus nerve. Immunocytes in these heterogeneous pathways express functional receptors for various neurotransmitters and many produce and excrete neurotransmitters themselves. Conversely, cytokine-specific receptors have been localized to nerves that produce cytokine-specific neuronal responses when activated, feeding the brain’s integrative centers with positionally and temporally precise information. While chondrocytes, bone cells and synoviocytes express neurotransmitter receptors that contribute to phenotype and function, much about how these three differently specialized systems functionally interact remains unknown. Neurotransmitters like substance P, CGRP, adenosine, endocannabinoids, serotonin, acetylcholine and norepinephrine have all been shown to have strong modulating activities on joint inflammation and destruction in rheumatic disorders. Acetylcholine receptor knockout and vagotomy cause bone loss in otherwise healthy animals, while β2-adrenoceptor deficiency results in the opposite. Furthermore, nerve ending within the joints have been observed class switching to release alternative neurotransmitters in a disease-dependent manner and stimulating the vagus nerve in rheumatic humans and rodents has been shown to reduce clinical score, joint inflammation and destruction, and even reverse erosive damage.
We hope this Research Topic will increase the global knowledge about innate neuro-osteo-immune crosstalk and its influence on bone and joint outcomes in injury and disease. We aim to capture the most recent mechanistic insights, innovative ideas, and potential therapeutic approaches that influence these systems to better treat diseases that affect the cartilage, bone and synovial tissues.
We welcome the submission of Original Research, Clinical Trials, Reviews, and Opinion articles covering, but not limited to, the following topics:
• Mechanistic studies of systemic neural control over bone/cartilage turnover and inflammation in the joint
• Anatomy and role of local innervation in joint homeostasis
• Functional neurotransmitter-based crosstalk between immune and bone/cartilage cells and the role of immunocyte derived neurotransmitters in the rheumatic joint
• Preclinical or clinical studies of nerve stimulation with joint inflammation or bone/cartilage preservation outcome
It has become clear that there is another contributor, moderator, and sometimes conductor of this intricate localized crosstalk, namely the peripheral nervous system with its sensory and autonomic branches, and by extension, neurotransmitters that make up the neural vocabulary. The bidirectional interaction and integration of the nervous and immune systems to affect immunologic homeostasis is well established and have been partly mapped into distinct circuits and reflexes, particularly those involving the vagus nerve. Immunocytes in these heterogeneous pathways express functional receptors for various neurotransmitters and many produce and excrete neurotransmitters themselves. Conversely, cytokine-specific receptors have been localized to nerves that produce cytokine-specific neuronal responses when activated, feeding the brain’s integrative centers with positionally and temporally precise information. While chondrocytes, bone cells and synoviocytes express neurotransmitter receptors that contribute to phenotype and function, much about how these three differently specialized systems functionally interact remains unknown. Neurotransmitters like substance P, CGRP, adenosine, endocannabinoids, serotonin, acetylcholine and norepinephrine have all been shown to have strong modulating activities on joint inflammation and destruction in rheumatic disorders. Acetylcholine receptor knockout and vagotomy cause bone loss in otherwise healthy animals, while β2-adrenoceptor deficiency results in the opposite. Furthermore, nerve ending within the joints have been observed class switching to release alternative neurotransmitters in a disease-dependent manner and stimulating the vagus nerve in rheumatic humans and rodents has been shown to reduce clinical score, joint inflammation and destruction, and even reverse erosive damage.
We hope this Research Topic will increase the global knowledge about innate neuro-osteo-immune crosstalk and its influence on bone and joint outcomes in injury and disease. We aim to capture the most recent mechanistic insights, innovative ideas, and potential therapeutic approaches that influence these systems to better treat diseases that affect the cartilage, bone and synovial tissues.
We welcome the submission of Original Research, Clinical Trials, Reviews, and Opinion articles covering, but not limited to, the following topics:
• Mechanistic studies of systemic neural control over bone/cartilage turnover and inflammation in the joint
• Anatomy and role of local innervation in joint homeostasis
• Functional neurotransmitter-based crosstalk between immune and bone/cartilage cells and the role of immunocyte derived neurotransmitters in the rheumatic joint
• Preclinical or clinical studies of nerve stimulation with joint inflammation or bone/cartilage preservation outcome
Keywords: Bone; Joints; Autonomic Nervous System; Neurotransmitters; Inflammation;
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
