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.
