Bone mass reflects the coupled balance of activity of osteoblasts to synthesize and osteoclasts to degrade bone matrix. Coupling of the activity between these two lineages is required for balance in bone remodeling, and dysregulation of this process is a major mechanism in the pathogenesis of many of human skeletal disorders, such as osteoporosis, inflammation-induced bone loss, and periodontitis. Additionally, osteoblast differentiation capacity of skeletal stem cells must be tightly controlled, as inadequate bone formation results in low bone mass, skeletal fragility, and bone healing defect, while over-exuberant osteogenesis results in extra-bone formation in the soft connective tissues, such as trauma-induced heterotopic ossification and fibrodysplasia ossificans progressiva by a genetic mutation. Understanding the molecular mechanisms that regulate these activities is a key to developing improved therapeutics to treat human skeletal disorders. To this end, we took advantage of an unbiased high-throughput screens to identify new proteins that control osteoblast and osteoclast commitment, differentiation, and activation under pathological conditions. Alternatively, using the premise that tissues emerging from similar points during vertebrate evolution may share common intracellular signaling networks to guide their activity, we have sought to leverage our extensive knowledge obtained from the immune system to understand the mechanism in which bone cells are regulated.
