Synthesis and characterization of a lubricin mimic (mLub) to reduce friction and adhesion on the articular cartilage surface

The lubricating proteoglycan, lubricin, facilitates the remarkable low friction and wear properties of articular cartilage in the synovial joints of the body. Lubricin lines the joint surfaces and plays a protective role as a boundary lubricant in sliding contact; decreased expression of lubricin is associated with cartilage degradation and the pathogenesis of osteoarthritis. An unmet need for early osteoarthritis treatment is the development of therapeutic molecules that mimic lubricin function and yet are also resistant to enzymatic degradation common in the damaged joint. Here, we engineered a lubricin mimic (mLub) that is less susceptible to enzymatic degradation and binds to the articular surface to reduce friction. mLub was synthesized using a chondroitin sulfate backbone with type II collagen and hyaluronic acid (HA) binding peptides to promote interaction with the articular surface and synovial fluid constituents. In vitro and in vivo characterization confirmed the binding ability of mLub to isolated type II collagen and HA, and to the cartilage surface. Following trypsin treatment to the cartilage surface, application of mLub, in combination with purified or commercially available hyaluronan, reduced the coefficient of friction, and adhesion, to control levels as assessed over macro-to micro-scales by rheometry and atomic force microscopy. In vivo studies demonstrate an mLub residency time of less than 1 week. Enhanced lubrication by mLub reduces surface friction and adhesion, which may suppress the progression of degradation and cartilage loss in the joint. mLub therefore shows potential for treatment in early osteoarthritis following injury.     

Osteoarthritis today: Lost in translation?

Osteoarthritis (OA) is a highly prevalent joint disease that is associated with pain, loss of function, and high direct and indirect economic costs. The current therapeutic options are inadequate, providing only a moderate symptom relief without the possibility of disease modification. While treatment options and personalized medicines are increasing for many complex diseases, OA drug development has been impeded by the advanced state of disease at the time of diagnosis and intervention, heterogeneity in both symptoms and rates of progression, and a lack of validated biomarkers and relevant outcome measures. This review article summarizes the OA landscape, including therapies in development as potential OA treatments, potential biomarkers undergoing evaluation by the US Food and Drug Administration, and a summary of current OA treatment guidelines, with a particular focus on the knee OA.