Osteoblastogenesis and Role of Osteoblasts in Calcium Homeostasis and Remodeling of Bone

Bone remodeling is very important for repair of microfractures and fatigue damage and prevention of excessive aging and its consequences. Bone remodeling lasts for about 6-9 months. During this period osteoclasts resorb damaged bone and osteoblasts synthesize new bone. The lifespan of mature osteoclasts is about 15 days and for osteoblasts 3 months. Therefore, the time required for the remodeling of a given segement of bone is much longer than the lifespan of its cells which perform remodeling. A supply of new osteoblasts and osteoclasts are therefore needed for succesful remodeling by the basic multicellular unit. The major event that triggers osteogenesis is the transition of mesenchymal stem cells into bone differentiating osteoblast cells. Osteoblast commitment and differentation are controlled by complex activities. Many factors are involved in the regulation of osteoblastogenesis. Bone morphogenetic proteins and the Wnt glycoproteins play crucial roles in signaling osteoblast commitment and differentiation, and are the only known factors capable of initiating osteoblastogenesis from uncommitted progenitors. They can initiate commitment of mesenchymal cells to osteoblastic lineage. The initial cell division is asymmetric, giving rise to another stem cell and a committed osteoprogenitor. After commitment to the osteoblastic lineage, a osteoprogenitor cell gives rise to the transit-amplifying compartment. At this stage osteoprogenitor cells proliferate intensively. After this stage, the cells are more differentiated and give rise to preosteoblasts which express both STRO1, alkaline phosphatase, pyrophosphate, and type 1 collagen. Preosteoblasts are committed to the osteoblast lineage with extensive replicative capacity, but have no self-renewal capacity. Preosteoblasts form the intermediate stage of osteoblastogenesis. The mature osteoblasts express osteopontin, alkaline phosphatase, bone sialoprotein, and osteocalcin. This stage is responsible for the laying down of bone. Mature osteoblasts have limited replicative potential. About 65% of mature osteoblasts and a proportion of cells in the transient amplifying compartment terminate in apoptosis. Apoptosis is a critical determinant of osteoblast number in the basic multicellular unit. The terminal stage of the bone lineage is the post-mitotic osteocyte which is embedded within the advancing osteoid. A minor component of mature osteoblasts differentiate into lining cells of the bone. Lining cells line the quiscent bone with no remodeling activity. Bone morphogenetic proteins, Wnt glycoproteins, Hedgehog proteins, PPARgama ligands, and transcription factors such as Runx 2 and Osterix play important roles in these critical steps of osteoblastogenesis and bone remodelling.