Osteogenesis

Definition

Osteogenesis is the process of bone tissue formation by multipotent stem cells of the third germ layer-origin - the mesoderm. A stem cell at an early stage of osteogenic development, after receiving a differentiation signal, becomes a bone tissue progenitor cell and loses the ability to differentiate into other cells of mesenchymal origin. Osteogenesis is started during embryonal development (around week 8) and ends when the organism reaches maturity; in humans it occurs between the ages of 20 and 25. The process of osteogenesis arising on the basis of the embryonic connective tissue (mesenchyme) is called ossification on the connective tissue substrate and takes place mainly during the formation of flat bones of the skull, mandible, maxilla and collarbones. In turn, for the growth of the long and short bones, and the natural healing of fractures is responsible osteogenesis on the cartilage basis. There are two main populations of bone cells with complementary activities - bone-forming cells (osteoblasts, osteocytes) and bone resorbing cells (osteoclasts). Osteoblasts are the precursor cells of osteogenesis. Osteoblasts are originate from two embryonic cell populations: mesenchymal stromal cells or mesenchymal stem cells (MSCs) . The differentiation of MSCs into osteoblasts depends on the activity of many cytokines and growth factors (e.g. BMP, TGF-β, FGF, IGF) and on the activation of transcription factors inducing the osteogenesis process (Osterix, Runx2 ) . MSC differentiate into osteoblasts, which produce type I collagen and proteoglycans that form the extracellular matrix of bone tissue. Osteoblasts also produce proteins and glycoproteins involved in bone mineralization: osteonectin, osteocalcin, and osteopontin. After the maturation process, osteoblasts form osteocytes and their function is primarily the exchange of nutrients and metabolites. Moreover, osteoblasts indirectly regulate the formation of osteoclasts responsible for bone resorption and remodeling through osteoblast-to-osteoclast communication, paracrine signaling, and cell-bone matrix interaction. Maintaining a balance in the activity of osteoblasts and osteoclasts is essential in bone homeostasis and in the process of bone remodeling, and in the bone fractures repair. An imbalance in their activity leads to diseases such as osteoporosis and Paget's disease, which have a significant impact on the quality of life of patients.