14. Osteogenesis (ossification). Types and structural characteristics.

Osteogenesis is the formation of bone. It is the process of laying down new bone material by osteoblasts. 

Development of the skeleton begins in the early embryo and foetus. Growth continues after birth and up to adolescence. Bones are formed by either intra-membranous or endochondral ossification. 

Intra-membranous ossification occurs in areas of ordinary mesenchyme where osteoblasts differentiate directly within richly-vascularised mesenchymal connective tissue. Flat bones of the cranium, part of the mandible, and clavicles develop via Intra-membranous ossification.

Endochondral ossification is when mesenchymal cells differentiate into cartilage, and this cartilage is later replaced by bone. Most long bones, vertebral column, ribs, and pelvis develop via endochondral ossification.

Both types of osteogenesis have the same mechanism of bone matrix deposition and mineralization by producing spongy bone first. Then this bone later develops into dense bone.

Intramembranous bone formation begins during development when mesenchymal cells aggregate at sites of richly-vascularised connective tissue and differentiate into osteoblasts. They secrete collagen, osteoid and alkaline phosphatase, which induces mineralization of osteoid. 

Hydroxyapatite is the dominant mineral of the bony matrix. Morphological changes in the mesenchymal stem cells begin to occur: the cell body becomes larger and rounder; the long thin cell processes are no longer present; and the amount of Golgi apparatus and RER increases. 

During ossification, osteoblasts are trapped in the matrix and become osteocytes which reside in small spaces called lacunae and are connected with neighbouring osteocytes by processes that lie in small channels called canaliculi. Here trabeculae of newly formed bone are initially laid down. Trabeculae thicken and merge to produce a three- dimensional lattice of spongy bone. 

Loose, highly vascularised, hematopoietic connective tissue becomes bone marrow. Osteoclasts migrate to trabeculae surfaces to begin resorbing bony matrix, which provides a mechanism for constant bone remodelling.

In fracture healing, endochondral osteogenesis is the most common occurring process. Endochondral ossification involves the formation of cartilage tissue from mesenchymal cells, and the subsequent replacement of cartilage tissue by bone.

The first site of ossification occurs in the primary centre of ossification, which is in the middle of diaphysis. The following stages then occur: 

1. Formation of periosteum: The perichondrium becomes periosteum. The periosteum contains a layer of osteoprogenitor cells, which later become osteoblasts.

2. Formation of bone collar: The osteoblasts secrete osteoid against the shaft of the cartilage model, this serves as support for the new bone.

3. Calcification of the matrix: The chondrocytes in the centre of ossification begin to grow and die. From the periosteum, blood vessels invade the diaphysis and bring in mesenchymal and osteoprogenitor cells. 

Incoming blood vessels carry in bone marrow cells. Proliferation of remaining chondrocytes causes the epiphyses to increase in length. They eventually form the epiphyseal plate. 

Toward the end of foetal life and continuing into puberty, ossification centres appear in the two epiphyses of long bones. After adolescence, growth plates close and growth is ceased.