The biological events associated with inflammation are intimately intertwined with the musculoskeletal system. Inflammation plays a critical role in the healing process of all musculoskeletal tissues and although it is important for optimal healing to occur, any disruption or extension of this stage of healing may lead to deleterious effects and prolonged healing. For example, inflammation is the first stage of fracture healing; if this stage is blocked or interfered with, fracture union does not progress. The processes of formation and remodelling of all musculoskeletal tissues are governed not only by the host's genome, but also by mechanical and biological cues in the local microenvironment, including the relative amounts of different pro- and anti-inflammatory cytokines, growth factors and other molecules. These processes continue throughout the host's lifetime, providing the necessary phenotype to adapt to the ever-changing milieu in which the host must function. Therefore, it is imperative to control the inflammatory stage to optimise the healing process.
This special issue of the Journal of Orthopaedic Translation concentrates on highly relevant translational topics that underscore the important link between inflammation and the musculoskeletal system.
Gallo et al. review the fundamental concepts that are relevant to the musculoskeletal system in health and disease. In particular, the authors recognize the significance of inflammation and immune processes in mitigating adverse stimuli (bacterial invasion, trauma etc.), while facilitating reparative and regenerative processes. This information is critical to the prevention of chronic inflammation (which can lead to the destruction of tissues in all organ systems including the musculoskeletal system), and for the development of core principles for tissue engineering and regenerative medicine. Macrophages are the key cells that, regulate inflammation and tissue repair. Shi et al. review the role of macrophages during bone healing, particularly during the initial inflammatory phase, leading to the development of the field of osteoimmunology. Although there are numerous sources of inflammatory factors produced during healing, macrophages are certainly one of the most important sources and regulators of inflammation. Research in this novel field may aid researchers in developing treatment strategies to control the inflammatory phase of bone healing.
Orthopaedic implants (e.g. hip and knee replacements, devices for fracture and spinal fixation and many others) have revolutionized the treatment of numerous musculoskeletal conditions. Some of the dreaded complications associated with these devices, however, include infection of the implant, and loss of fixation with implant loosening. Wasko et al. highlight the biological principles associated with well-functioning orthopaedic implants and the consequences of infection and chronic inflammation. Takagi et al. tackle the problem of distinguishing septic (infectious) versus aseptic loosening of implants, a topic with which they have enormous expertise. By understanding and distinguishing these different biological processes, the clinician can make the appropriate diagnosis and then provide the patient with the optimal plan for treatment. Furthermore, a clearer appreciation of these concepts will hopefully provide opportunities for improvement of implant design, preventative measures, and patient outcome.
Gibon et al. then summarise the literature that is currently known about inflammation and bone homeostasis, and the effects of aging. With increasing age, individuals are subjected to a relatively increased baseline pro-inflammatory environment compared to younger individuals. This relative pro-inflammatory milieu can be associated with dysregulated tissue formation and repair, especially in the scenario of chronic inflammation (e.g. an elderly patient involved in a multiple trauma). In this regard, potential interventions to modulate inflammation and improve subsequent reconstructive processes would be a welcomed advancement.
Low back pain is one of the most prevalent musculoskeletal disorders and one of the leading causes of disability. Degenerative disc disease is considered the most common cause of low back pain and unlike other musculoskeletal disorders it affects a considerable portion of younger populations. As a result, the socio-economic burden is large. Erwin et al. discuss how irregular inflammatory processes may contribute to intervertebral disc degeneration. The authors advocate the careful control of the inflammatory phase to trigger the correct healing response and create a suitable micro-milieu for stem cells and biomaterials used for intervertebral disc regeneration.
Cheung et al. discuss how sarcopenia (progressive loss of muscle mass and strength) is greatly affected by increased inflammation and inflammatory pathways. Inflammation tips the careful balance between muscle synthesis and proteolysis towards the latter, causing muscle degradation. As previously mentioned, ageing increases baseline inflammation and this is discussed further with relation to sarcopenia pathogenesis. Methods to reduce inflammation and regulate the inflammatory mechanisms are discussed in relation to preventing sarcopenia.
A similar imbalance is observed in osteoporosis in which there is an imbalance between bone formation and bone resorption. Moreover, this imbalance leads to osteoporosis, commonly observed in the elderly, which often results in fractures that impose a major burden on individuals and society. Ren et al. demonstrate how inflammation may play a role in bone resorption, which may contribute to the development of osteoporosis and how this relates to the G protein-coupled receptor 1.
This issue also includes a number of translational articles related to the topic of inflammation and the musculoskeletal system exploring the role of CYR61 and angiogenesis, the importance of neurons for bone metabolism, the administration of trolox to reduce tendon adhesion and promising progress on the use of magnesium implants to enhance fracture healing.
The editors of this special issue of JOT are pleased to provide the reader with important information concerning inflammation and the musculoskeletal system that is both fundamental and highly translational, for the ultimate purpose of expanding our knowledge base and improving patient care.