Osteoarthritis (OA) is a well-known disease that is part of the aging process and also one of the most common diseases among mammals. Although this musculoskeletal disorder has been described in mammals of many ages, having been reported in Egyptian mummies and in dinosaurs, its exact etiology is far from being fully understood. With the graying of the world population, it is of the utmost importance to find out more about the pathogenesis of the disease and thus allow the discovery of new treatments to stop or prevent its progression. A number of risk factors have lately been identified (1). Mechanical factors, among others, are likely to play a very important role in the initiation of the disease process. Endogenous factors such as type II collagen mutation or dysplastic conditions are also known to be involved in initiating the OA process (2). There is now strong evidence that the structural changes globally observed in OA are due to a combination of factors, ranging from the mechanical to the biochemical (3,4). The disease process affects not only the cartilage, but also the entire joint structure, including the synovial membrane, subchondral bone, ligaments, and periarticular muscles. In OA synovium, the inflammatory changes that take place include synovial hypertrophy and hyperplasia with an increased number of lining cells, and also an infiltration of the sublining tissue with a mixed population of inflammatory cells. In patients with severe disease, the extent of inflammation can sometimes reach that observed in rheumatoid arthritis (RA) patients at the clinical stage (5,6). Some degree of synovitis has also been reported in even the early stages of the disease (7). Synovial inflammation is clearly reflected in many of the signs and symptoms of OA, including joint swelling and effusion, stiffness, and sometimes redness, particularly at the level of the proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1529-0131%28200106%2944%3A6%3C1237%3A%3AAID-ART214%3E3.0.CO%3B2-F

Osteoarthritis, an inflammatory disease: Potential implication for the selection of new therapeutic targets

http://www.uef.sav.sk/Soltes_PDF/2007%20Biotechnol.Adv.%20-%20Stern.pdf

The many ways to cleave hyaluronan.

Hyaluronic acid (HA) is a commercially valuable medical biopolymer increasingly produced through microbial fermentation. Viscosity limits product yield and the focus of research and development has been on improving the key quality parameters, purity and molecular weight. Traditional strain and process optimisation has yielded significant improvements, but appears to have reached a limit. Metabolic engineering is providing new opportunities and HA produced in a heterologous host is about to enter the market. In order to realise the full potential of metabolic engineering, however, greater understanding of the mechanisms underlying chain termination is required.

Microbial hyaluronic acid production

Hyaluronic acid (HA), is a polyanionic polysaccharide that consists of N-acetyl-D-glucosamine and beta-glucoronic acid. It is most frequently referred to as hyaluronan because it exists in vivo as a polyanion and not in the protonated acid form. HA is distributed widely in vertebrates and presents as a component of the cell coat of many strains of bacteria. Initially the main functions of HA were believed to be mechanical as it has a protective, structure stabilizing and shock-absorbing role in the body. However, more recently the role of HA in the mediation of physiological functions via interaction with binding proteins and cell surface receptors including morphogenesis, regeneration, wound healing, and tumor invasion, as well as in the dynamic regulation of such interactions on cell signaling and behavior has been documented. The unique viscoelastic nature of hyaluronan along with its biocompatibility and nonimmunogenicity has led to its use in a number of cosmetic, medical, and pharmaceutical applications. More recently, HA has been investigated as a drug delivery agent for ophthalmic, nasal, pulmonary, parenteral, and dermal routes. The purpose of our review is to describe the physical, chemical, and biological properties of native HA together with how it can be produced and assayed along with a detailed analysis of its medical and pharmaceutical applications.

https://www.tandfonline.com/doi/pdf/10.1080/10717540590952555

Hyaluronan: Pharmaceutical Characterization and Drug Delivery

Degradative action of reactive oxygen species on hyaluronan.

Assay of synovial fluid parameters: hyaluronan concentration as a potential marker for joint diseases.

Effects of oxygen-derived free radicals on the molecular weight and the polydispersity of hyaluronan solutions

Hypoxanthine-guanine-phosphoribosyltransferase (HGPRT; EC 2.4.2.8) was determined as an enzyme following an ordered bireaction in the presence of substrate inhibition due to hypoxanthine. This kind of inhibition has not been postulated for HGPRT so far. The mechanism and the kinetic constants of the reaction of HGPRT from Saccharomyces cerevisiae were investigated by initial velocity studies involving a non-linear regression analysis. In addition, two kinds of experimental designs were compared: the variation of hypoxanthine concentrations over wide ranges at different of fixed levels of 5-phosphoribosyl-1-pyrophosphate, and the use of five appropriate sets of experimental conditions each characterized by different hypoxanthine and 5-phosphoribosyl-1-pyrophosphate concentrations. Both experimental designs were consistent with an ordered bi bi mechanism including a dead-end-complex between the enzyme and hypoxanthine.

Barbara M. Praest

Papers

Assay of synovial fluid parameters: hyaluronan concentration as a potential marker for joint diseases.

Effects of oxygen-derived free radicals on the molecular weight and the polydispersity of hyaluronan solutions

Substrate inhibition in an enzymatic ordered bireactant system: non-linear modelling of the kinetics of hypoxanthine-guanine-phosphoribosyltransferase