Relevance of osteal macrophages in bone remodeling

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The bone matrix is constantly remodelled through the activities of bone-forming osteoblasts and bone-resorbing osteoclasts, and a relative increase of bone resorption over bone formation can result in osteoporosis, one of the most prevalent diseases of the aged population. Our previous analysis of two different osteoporotic mouse models has suggested that specific cytokines, such as Ccl5 and Il33, may be involved in the regulation of bone remodelling. To analyze this possibiliy we will study the effects of both cytokines on bone cells in vitro, and we will study genetically engineered mouse models with altered expression of either Ccl5, Il33 or their receptors. In addition, we will analyze, which cell types within the bone microenvironment are the source of both cytokines and perform cocultureexperiments of bone-forming osteoblasts and osteal macrophages to uncover some of the molecular mechanisms underlying the interactions between bone and immune cells. Taken together, this project should not only add significant information to the emerging field of osteoimmunology, but also identify novel target proteins for the treatment of bone loss disorders, such as osteoporosis, metastatic bone disease or osteoarthritis.