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Lubricating Cartilage: exploring the relation between lubrication and gene-regulation to alleviate osteoarthritis

Periodic Reporting for period 2 - CartiLube (Lubricating Cartilage: exploring the relation between lubrication and gene-regulation to alleviate osteoarthritis)

Reporting period: 2019-03-01 to 2020-08-31

The main issue being addressed by this project is to determine whether, by lubricating articular cartilage of osteoarthritic joints, it is possible to alleviate the disease (osteoarthritis, OA)).

It is important for society because OA is a very widespread, painful and debilitating disease, with over 30M sufferers in the EU alone, which imposes a high burden both in terms of human suffering and in socio-economic terms. As it is a disease which afflicts mostly the elderly population (>50% of people over 70) it reduces their mobility and ability to participate in society, while at the same time imposing a high medical and economic cost in terms of expending of treatment resources and lost working ability.

The project consists on the one hand of developing and improving suitable lubricants for injection into joints (intra-articular or IA injections), and in parallel developing means of evaluating whether such IA administration of lubricants leads to changes in the cartilage that indicate the lubrication is having a beneficial effect, as well as relieving pain. Experiments are carried out on a mouse model. The overall objectives are to determine the optimum lubricant and means of applying it to joints while maximizing its beneficial effects on the OA joints.
In the project to date (half-way point) we have progressed on several fronts, and ten papers have so far been published.
The work performed so far focused on elucidating the microscopic details of hydration lubrication in systems relevant to joint lubrication. These included direct surface force balance (SFB) studies on different boundary layer combinations, including those of lipid and lipid mixtures that are believed to be active in articular cartilage boundary lubrication; the synergy between hyaluronan (hyaluronic acid) and lipids which is believed to be central for such boundary effects; the effect of different biomedically-important molecules such as polyethylene oxide on lubrication by lipids; very importantly, the nature of phosphocholinated liposomes which are both sterically-stabilized and also provide excellent lubrication, and are the major candidates for our work with the Oxford group (team-member Tonia Vincent and her co-workers). Some of our most exciting (as yet unpublished results) were obtained in connection with gene regulation in chondrocytes by our IA injected lubricants with the Oxford team.
We have certainly progressed beyond the state-of-the-art in determining the effect of lipid mixtures as opposed to single component lubricating vesicles; in creating superlubrication vectors stabilized by novel polyphophocholinated moeities; and in demonstrating the effect of these on gene regulation in the cartilage cells (chondrocytes).

Expected results to be obtained by the end of the project include our current work on the effect of lubricants IA-injected into mice with OA, from the point of view both of morphology and gene regulation, and possibly reduction in pain level, all on murine models.