BONE OSSIFICATION

Bone Ossification is the process of bone formation, also called as Osteogenesis. This process begins from the stage of embryonic development and continues until early adulthood. The skeleton begins to develop within the first few weeks of conception and by the end of eight weeks after conception the skeleton framework is formed in cartilage and connective tissue membranes. After which Ossification takes place, there are two types of Ossification- Intramembranous & Endochondral Ossification. Both of these processes begins with the mesenchymal tissue precursor but they differ in the way they are transformed in to a bone

• Intramembranous Ossification: In this process, there is a direct calcification of undifferentiated connective tissue membrane that develops into a bone in fetus. It begins with the differentiation of neural crest mesenchymal cells into specialized bone forming cells, which is the point or center of Ossification. The flat bones of the skull, mandible, clavicle and most of the cranial bones are developed through Intramembranous Ossification
• Endochondral Ossification: This process begins with the transformation of the mesoderm-derived mesenchymal cells that differentiates into chondrocytes. Chondrocytes proliferate rapidly and secrete an extra-cellular matrix to form a cartilage model called the hyaline cartilage, which are later replaced by the bone. This process is also called as Intracartilagenous Ossification and the bones formed are called as endochondral bones. In this process during the third month of conception, the perichondrium that surrounds the hyaline cartilage models become infiltrated with the blood vessels and osteoblasts to become the periosteum.
• The primary ossification center is formed when the osteoblasts form a collar of the compact bone around the diaphysis. At the same time, the cartilage in the center begins to disintegrate and the osteoblasts penetrate in the disintegrating cartilage and replaced with spongy bone. Ossification continues from the center towards the end of the bones. Once the Spongy bone is formed in the diaphysis, Osteoclasts break down the newly formed bone that opens and develops into the medullary cavity
• The Secondary Ossification center is formed in the epiphysis as the cartilage continues to grow and increase the bone in length later, usually after birth. When the secondary ossification is complete, the hyaline cartilage is totally replaced by the bone except in two areas (i) A region of hyaline cartilage remains over the surface of the epiphysis as “Articular Cartilage” and (ii) another area of cartilage remains in the “epiphyseal plate or the growth Zone” (between the epiphysis and diaphysis). The Long bones and the remaining axial skeleton bones are formed by endochondral Ossification process.

Cells Involved in Ossification: There are four types of cells that are responsible for the ossification in bones. They are Osteochondroprogenitor cells, Osteoblasts, Osteocytes and Osteoclasts.

• Osteochondroprogenitor cells: These are mesenchymal stem cells that differentiates in to Chondrocytes, which are precursors of Osteoblasts and necessary for the development of bone
• Osteoblasts: Osteoblasts are bone forming cells that develop when Osteogenic cells differentiate in the periosteum (tissue covering the outer surface of the bone) and endosteum of the marrow cavity. They form ring or closely packed membrane on the surface of the bone, from which cellular processes begins to expand through the developing bony matrix. The Osteoblasts produce substances like growth factors, enzymes (alkaline phosphatase &collagense) and hormones (Osteocalcin& collagen). This part of the organic unmineralized component of bone matrix is called Osteoid. The osteoblast is thus formed surrounded by the growing bone matrix
• Osteocytes: Eventually osteoblast calcifies to form a hardened bony matrix and the cells get trapped in a space called lacuna.After the bone is completely ossified, the entrapped cells become a mature bone cell (Osteocyte). The calcium phosphate secreting channels are retracted leaving tiny canals in the bone matrix called as canaliculi. These canaliculi provide nutrients to the newly transformed osteoblasts, now termed as Osteocytes. Osteocytes are responsible for the regular maintenance of the bone
• Osteoclasts: Osteoclasts are large multinucleated cells responsible for bone remodeling (dissolution and absorption of bone). Osteoclasts are the mediators to continuous destruction of the bone for three reasons (i) to repair the bone after a break or Injury, as the destroyed portion of the bone protrude and makes bone reformation difficult (ii) to maintain equilibrium of the bone tissue i.e. to obtain only the necessary minerals used for growing the bone and the remaining calcium and phosphorous liberated by the broken down bone are released into the blood stream (iii) As the bone grows the shape changes and Osteoclasts are necessary to dissolve the part of the bone that causes disfigurement or changes in bone.