Osteoarthritis as an organ disease: from the cradle to the grave

Abstract

Considered for decades as a cartilage disease, recent studies of osteoarthritis (OA) take us back to the concepts discussed at the naming of the disorder as "bone-joint-inflammation". By describing the joint as an organ, can OA be called an organ disease-similar to heart disease? Is there a systemic (which system?) involvement? Would this help with diagnosis or therapy? Hyperplasia of the joint tissues is one of the most notable early features of the disease: articular cartilage thickens, chondrocytes proliferate and increase matrix biosynthesis, but not its incorporation; the subchondral bone densifies but is hypomineralised and there is an increase in bone marrow fat content. Associations between OA and hypertension, hypercholesterolaemia and blood glucose suggest systemic and metabolic components are involved. The source of pain is still unknown but there is evidence for peripheral and central sensitisation. Joint deformity is difficult to quantify, but statistical shape modelling provides a tool to use as an imaging biomarker. A genome-wide association study metaanalysis has identified novel genes associated with hip shape with many genes related to tissue growth and development. There are associations between hip shapes and age of first walking as well as with obesity through adulthood. These life-course events and a recapitulation in old age of developmental processes suggest that the cradle may affect our path to the grave. These observations suggest that tissue regeneration approaches, treating only the cartilage in OA joints, may only be of limited benefit.

Immunomodulation of MSCs and MSC-Derived Extracellular Vesicles in Osteoarthritis

“…The traditional viewpoint is that OA is a non-inflammatory disease. However, studies have shown that there is a type of chronic, low-grade inflammation in the pathogenesis of OA, which seriously hinders the proliferation of chondrocytes and the deposition of cartilage matrix, resulting in low efficiency of repair (Aspden and Saunders, 2019 ; Chow and Chin, 2020 ; Woodell-May and Sommerfeld, 2020 ). Various immune cells have been identified in the synovium of OA patients.…”

Intraarticular Ligament Degeneration Is Interrelated with Cartilage and Bone Destruction in Osteoarthritis

“…Joints represent a functional unit, which can be understood as an organ, and for this reason, OA is a whole joint disease [15]. This concept [15] is well accepted [16,17]. It describes that inflammation extends to all joint-associated structures including the joint capsule with the synovial membrane, intraarticular fat pads, menisci, and ligaments.…”

Zebrafish Models of Human Skeletal Disorders: Embryo and Adult Swimming Together

“…Several studies on human osteoarthritis (OA) have been addressed to the genetic component of the disease [44, 45]. In this context, zebrafish represents a powerful model to study the role of candidate genes in AO pathogenesis.…”