Proteomics in bone research

Abstract

Osteoporosis is prevalent among the elderly and is a major cause of bone fracture in this population. Bone integrity is maintained by the dynamic processes of bone resorption and bone formation (bone remodeling). Osteoporosis results when there is an imbalance of the two counteracting processes. Bone mineral density, measured by dual-energy x-ray absorptiometry has been the primary method to assess fracture risk for decades. Recent studies demonstrated that measurement of bone turnover markers allows for a dynamic assessment of bone remodeling, while imaging techniques, such as dual-energy x-ray absorptiometry, do not. The application of proteomics has permitted discoveries of new, sensitive, bone turnover markers, which provide unique information for clinical diagnosis and treatment of patients with bone diseases. This review summarizes the recent findings of proteomic studies on bone diseases, properties of mesenchymal stem cells with high expansion rates and osteoblast and osteoclast differentiation, with emphasis on the role of quantitative proteomics in the study of signaling dynamics, biomarkers and discovery of therapeutic targets.

Figure 1. Cytokines/chemokines regulate osteoclast development

Most skeletal osteoclasts originate from circulating monocytes. These cells from osteoporotic patients were reported to have increased levels of bone resorption activity when induced into osteoclasts in vitro. Recruitment of circulating monocytes into bone is mainly conducted by chemokines, such as CCR3 ligand and RANTES. Recruited monocytes in bone are targets of a variety of cytokines, such as RANKL and M-CSF, which also regulates the osteoblast differentiation and function. Therefore, these chemokines and cytokines produced by marrow stromal cells and their derivative osteoblasts play key roles in bone remodeling. GC: Glucocorticoid; HSC: Hematopoietic stem cell; M-CSF: Macrophage colony-stimulating factor; OPG: Osteoprotegerin.

Figure 2. BMPs/Wnt signaling-regulated osteoblastogenesis via Runx2 and Osterix

BMP: Bone morphogenetic protein.