Understanding the contribution of the osteoblast lineage to cartilage and joint health.

Osteoarthritis (OA) is a major disabling disease in developed countries and with a more active and ageing population, its socio-economic impact can only increase.

OA is a multifactorial disease involving many of the tissues within the joint, where damage to any of these starts a cascade of events that culminate in further deterioration of the joint.

In the preliminary data I show how deletion of a single protein, PAR2, in the bone forming/sensing osteoblast lineage protects cartilage from damage during OA development, even 1-year after intervention. The data also shows that PAR2 plays an important role in bone formation and resorption.

I therefore hypothesise that, signalling from the osteoblast lineage controlling bone homeostasis impacts on articular cartilage chondrocytes, thus affecting cartilage health.

Therefore, this proposal is aimed at investigating how communication between cells of the osteoblast lineage and the articular cartilage chondrocytes impacts long-term cartilage maintenance and joint health.

To achieve this I propose to harness PAR2 biology to dissect this relationship, allowing the identification of key pathways instrumental in sustaining long-term joint health.

Specifically, I propose a combination of in vitro and in vivo studies with an intense ‘omics’ focus to address the following objectives: Examine PAR2-dependent control of bone homeostasis, to reveal the critical osteoblast lineage pathways that control cartilage maintenance. Determine the effect of the osteoblast lineage secretome on chondrocyte and articular cartilage health.

Elucidate and manipulate PAR2-dependent pathways linked to osteoblast control of cartilage maintenance.

This approach will provide valuable insight into the role of osteoblasts/osteocytes in cartilage maintenance, thus delivering a greater basic understanding of how the osteoblast lineage controls bone homeostasis and subsequently how it affects cartilage health.