Skeletal System (Ossification)
Mesodermal cells form most bones and cartilage. Initially an embryonic, loosely organised connective tissue forms from mesoderm throughout the embryo, referred to as mesenchyme. Neural crest cells that migrate into the pharyngeal arches are also involved in the development of bones and other connective tissues in the head and neck (see Chapters 41–44).
Bones begin to form in one of two ways. A collection of mesenchymal cells may group together and become tightly packed (condensed), forming a template for a future bone. This is the start of endochondral ossification (Figure 23.1). Alternatively, an area of mesenchyme may form a hollow sleeve roughly in the shape of the future bone. This is how intramembranous ossification begins.
Long bones form by endochondral ossification (e.g. femur, phalanges) and flat bones form by intramembranous ossification (e.g. parietal bones, mandible).
The cells of the early mesenchymal model of the future bone differentiate to become cartilage (chondrocytes). This cartilage model then begins to ossify from within the diaphysis (the shaft of the long bone). This is the primary centre of ossification, and the chondrocytes here enter hypertrophy (Figure 23.2). As they become larger they enable calcification of the surrounding extra-cellular matrix, and then die by apoptosis.
The layer of perichondrium that surrounded the cartilage model becomes periosteum as the cells here differentiate into osteoblasts, and bone is formed around the edge of the diaphysis. This will become the cortical (compact) bone (Figures 23.2 and 23.3).
Blood vessels invade the diaphysis and bring progenitor cells that will form osteoblasts and haematopoietic cells of the future bone marrow (Figure 23.3). Bone matrix is deposited by the osteo- blasts on to the calcified cartilage, and bone formation extends outwards to either end of the long bone (Figure 23.4). Osteoclasts also appear, resorbing and remodelling the new bony spicules of spongy (trabecular) bone.
When osteoblasts become surrounded by bone they are called osteocytes, and connect to one another by long, thin processes through the bony matrix.
The epiphyses (ends) of most long bones remain cartilaginous until the first few years after birth. The secondary centres of ossification appear within the epiphyses when the chondrocytes here enter hypertrophy, enable calcification of the matrix and blood vessels invade bringing progenitor cells that differentiate into osteoblasts (Figure 23.5). The entire epiphysis becomes ossified (other than the articular cartilage surface), but a band of cartilage remains between the diaphysis and the epiphysis. This is the epiphyseal growth plate (Figure 23.6).
The growth plates contain chondrocytes that continually pass through the endochondral ossification processes described above. A proliferating group of chondrocytes enter hypertrophy in a tightly ordered manner, calcify a layer of cartilage adjacent to the diaphysis, apoptose, and this calcified cartilage is replaced by bone. In this way the long bone continues to lengthen.
Bones grow in width as more bone is laid down under the periosteum. Bone of the medullary cavity is remodelled by osteoclasts and osteoblasts.
When growth ceases at around 18–21 years of age, the epiphy- seal growth plates are also replaced by bone (see Chapter 24).
The flat mesenchymal sleeves that create the templates of flat bones formed by intramembranous ossification contain cells that condense and form osteoblasts directly. Other cells here form capillaries. Osteoblasts secrete a collagen and proteoglycan matrix that binds calcium phosphate, and the matrix (osteoid) becomes calcified.
Spicules of bone form and extend out from their initial sites of ossification. Other mesenchymal cells surround the new bone and become the periosteum.
As more bone forms it becomes organised, and layers of compact bone form at the peripheral surfaces (aided by osteoblasts forming under the periosteum), whereas spongy trabeculated bone is constructed in between. Osteoclasts are involved in resorbing and remodelling bone here to give the adult bone shape and structure.
The mesenchymal cells within the spongy bone become bone marrow.
Fibrous, cartilaginous and synovial joints also develop from mesenchyme from 6 weeks onwards. Mesenchyme between bones may differentiate to form a fibrous tissue, as found in the sutures between the flat bones of the skull, or the cells may differentiate into chondrocytes and form a hyaline cartilage, as found between the ribs and the sternum. A fibrocartilage joint may also form, as seen in some midline joints, for example the pubic symphysis.
The synovial joint is a more complex structure, comprising multiple tissues. Mesenchyme between the cartilage condensations of developing limb bones, for example, will differentiate into fibroblastic cells (Figure 23.7). These cells then differentiate further, forming layers of articular cartilage adjacent to the developing bones, and a central area of connective tissue between the bones. The edges of this central connective tissue mass become the synovial cells lining the joint cavity (Figure 23.8). The central area degenerates leaving the space of the synovial joint cavity to be filled by synovial fluid. In some joints, such as the knee, the central connective tissue mass also forms menisci and internal joint ligaments such as the cruciate ligaments.
Pregnant women require higher quantities of calcium and phosphorus in their diet than normal because of foetal bone and tooth development. Maternal calcium and bone metabolism are significantly affected by the mineralising foetal skeleton, and maternal bone density can drop 3–10% during pregnancy and lactation, and is regained after weaning.
A lack of vitamin D, calcium or phosphorus will cause soft, weak bones to form as the osteoid is unable to calcify. This leads to deformities such as bowed legs and curvature of the spine. Weak bones are more vulnerable to fracture. This is called rickets. Other conditions that interfere with the absorption of these vitamins and minerals, or malnutrition during childhood will also lead to ric quired for calcium absorption across the gut.