Ossification Process and Bone Repair
Mechanisms
Bones form in two ways. A process known as intramembranous
ossification forms bones that develop from layers of connective tissue.
Flat bones such as those found in the skull develop through this
process. Endochondral ossification (from the word roots endo-,
meaning "within," and chondral, meaning "cartilage") is bone formation
from a hyaline cartilage blueprint or template, which determines the
future bone shape. Bones of the limbs and extremities develop through
endochondral ossification. For example, an infant's arm and leg bones
contain only small amounts of actual hard bone material; they are
primarily made of cartilage. As the child grows, bone replaces the
cartilage.
Ossification is the process of forming bone. You learned that there are
two types of ossification:
•
•
intramembranous ossification, which is direct synthesis of
bone by specialized stem cells (mesenchymal cells) from fibrous
connective tissue; and
endochondral ossification, which is synthesis of bone from a
(hyaline) cartilage template.
•
Intramembranous Ossification
Intramembranous ossification is the process that forms and repairs the
flat bones of the skull, clavicles and other irregularly shaped bones. In
some situations of bone repair and adaptation to excessive force,
intramembranous ossification generates new bone.
The process of intramembranous ossification involves multiple steps:
1.
2.
3.
4.
Increased vascularization.
Recruitment of mesenchymal stem cells
Differentiation
Secretion of osteoid
5. Mineralization
6. Formation of trabeculae
7. Formation of outer compact bone
First, the site for future bone formation increases in vascularization—
new blood vessels form near the site where the bones will
grow. Mesenchymal stem cells, which originate in the embryonic
mesoderm, become active and travel through the blood vessels to the
future site of bone formation. Chemical messages then cause the
mesenchymal stem cells to differentiate: they change into
osteoprogenitor cells, which may divide and differentiate into
osteoblasts. The osteoblasts deposit osteoid (the unmineralized bone
extracellular matrix) and are then trapped in the matrix, where they
differentiate into osteocytes. Inorganic salts in the blood travel through
the blood vessels to mineralize the bone matrix. As a result,
hydroxyapatite crystals form within the osteoid. On the interior of the
tissue, small clusters of bone begin to connect with other clusters to
form trabeculae. Osteoblasts near the surface of the bone deposit matrix
in organized lamellae and form a thin outer layer of compact bone.
The periosteum ("peri-" means "surrounding" and "osteum" means
"bone") is living membrane composed of fibrous connective tissue that
forms on the outside of the compact bone. Its inside layer has
osteoblasts for bone growth and repair.
Endochondral Ossification
Most bones of the skeleton below the skull develop through
endochondral ossification.
This process involves the following steps:
1.
2.
3.
4.
5.
6.
Formation of a cartilage template
Growth of the template
Differentiation
Vascularization
Calcification
Bone formation
The first step is formation of a hyaline cartilage template, which is the
shape of the desired new bone. The cartilage template grows in size and
thickens through the production of new chondroblasts at the
perichondrium. The perichondrium is the cartilage equivalent of the
periosteum. Chondroblasts differentiate into chondrocytes, which
produce chemical messages that stimulate the increase of vascular
supply at the perichondrium. This increase in vascular supply brings in
inorganic salts, which mineralize the central cartilage matrix.
Cartilage is laid down as a template that provides some mechanical
stability. This is like when designers and architects build a template out
of balsa wood, clay or foam because it is easy to quickly remodel and
manipulate those substances. Then, once the template is worked out,
they will remodel it using a stronger material. In bone, the 'model'
cartilage is remodeled over time and osteoblasts produce a full bone
matrix with new collagen and hydroxyapatite. In this way, biology works
more efficiently than any engineered tissue graft.