Genetic regulation of osteoclast development and function

Bone mass is controlled by the relative activities of osteoblasts, which are bone forming cells, and osteoclasts, which degrade the tissue.The osteoclast is a cell of haematopoietic origin and a member of the monocyte/macrophage lineage. Development of osteoclasts requires the concerted actions of a range of cytokines, steroids and lipids, which act directly on precursors themselves and indirectly by targeting a combination of mesenchymal supportive cells and those in the lymphoid lineage.The capacity of mature osteoclasts to resorb bone is cytokine driven and depends on their ability to recognize the matrix, polarize, and secrete protons and a collagenolytic enzyme.So far, most genetic mutations that regulate bone mass, whether natural or generated by targeted deletions, are associated with the osteoclast.Mutations can be inherent to the osteoclast and precursor, or found in proteins that are produced by lymphoid or mesenchymal tissue, which regulate the survival, differentiation and/or function of the mature bone-resorbing cell.Use of the data obtained in genetic studies has led to the development of several drugs that selectively suppress osteoclast function, thereby helping to maintain bone mass.