Osteoclasts and Remodeling Based Bone Formation

Osteoclasts are multinuclear cells of the monocyte macrophage lineage. They are responsible for bone remodeling by first resorbing packets of bone, which are subsequently replaced by new bone produced by osteoblasts. Osteoblasts are derived from mesenchymal stem cells, and thus osteogenesis can also be induced in various tissues at extra skeletal sites. Fifty years ago it was discovered that demineralized bone matrix is able to induce ectopic bone formation. Since that time the differentiation of bone cells has been studied intensively. The aim was to produce bone for the repair of bone defects. The molecular basis of bone remodeling has been established in great detail and the mechanism of how bone resorption and bone formation are coupled in bone remodeling sites has been delineated. Osteoclasts resorb bone, but they also secrete anabolic signals that induce mesenchymal stem cells and osteoblasts to initiate osteogenesis in resorption lacuna (remodeling) or another nonresorbed site (modeling). It is this osteoclast derived influence on mesenchymal stem cells and osteoblasts that could be utilized in tissue engineering. So far investigators have tried to find ways to induce bone formation by activating mesenchymal stem cells, but a better understanding of the remodeling paradigm of bone, the intrinsic regulation of bone formation through osteoclastic resorption, could be utilized for tissue engineering. Scaffold materials like decellularized natural tissue extracellular matrices or bone type resorbable mineral matrices induce resorption and simultaneously induce bone formation.