Introduction: Osteoarthritis (OA), a chronic, debilitating and degenerative disease of the joints, is the most common form of arthritis. The seriousness of this prevalent and chronic disease is often overlooked. Disease modifying OA drug development is hindered by the lack of soluble biomarkers to detect OA early. The objective of OA biomarker research is to identify early OA prior to the appearance of radiographic signs and the development of pain.
Areas covered: This review has focused on extracellular genomic material that could serve as biomarkers of OA. Recent studies have examined the expression of extracellular genomic material such as miRNA, lncRNA, snoRNA, mRNA and cell-free DNA, which are aberrantly expressed in the body fluids of OA patients. Changes in genomic content of peripheral blood mononuclear cells in OA could also function as biomarkers of OA.
Expert commentary: There is an unmet need for soluble biomarkers for detecting and then monitoring OA disease progression. Extracellular genomic material research may also reveal more about the underlying pathophysiology of OA. Minimally-invasive liquid biopsies such as synovial fluid and blood sampling of genomic material may be more sensitive over radiography in the detection, diagnosis and monitoring of OA in the future.
Chondrocytes are the main cells in the extracellular matrix and possess a highly differentiated phenotype that is hallmark of the unique physiological functions of articular cartilage. The plasma membrane of articular chondrocytes contains a rich and diverse complement of membrane proteins, known as the membranome, which defines the cell surface phenotype of the cells. The chondrocyte membranome is a key target of pharmacological agents and is important for function and includes channels, transporters, enzymes, receptors, and anchors for intracellular, cytoskeletal and extracellular matrix proteins and other macromolecular complexes. The chondrocyte channelome, is a sub-compartment of the membranome and includes a complete set of ion channels and porins expressed in these cells. Many of these are multi-functional proteins with ?moonlighting? roles, serving as channels, receptors and signalling components of larger molecular assemblies. The aim of this review is to summarise our current knowledge on the fundamental aspects of chondrocyte channelome, discuss its relevance to cartilage biology and highlight its possible role in the pathogenesis of osteoarthritis. Excessive and inappropriate mechanical loads, an inflammatory micro-environment, alternative splicing of channel components or accumulation of basic calcium phosphate crystals can result in the altered chondrocyte channelome function. Alterations in Ca2+ signalling may lead to defective synthesis of ECM macromolecules and aggravated catabolic responses in chondrocytes, which is an important and relatively unexplored aspect of the complex mechanism of osteoarthritis development.