Thursday, June 28, 2007

Bone cells

There are three types of functional cells in bone tissue:
osteoblasts, osteocytes and osteoclasts (Fig. 3.33).
Osteoblasts
Osteoblasts arise from mesenchymal stem cells present
in the stroma (framework) of the bone marrow. These
cells have the potential to differentiate into a variety of
mesenchymal tissues, such as bone, cartilage, tendon,
muscle, marrow, fat and dermis. The stem cells proliferate
and then commit themselves to a particular
pathway of lineage progression, differentiation and maturation (Bruder et al., 1994). The commitment
event and lineage progression involve the action of locally
generated cytokines and growth factors, many of
which are controlled by circulating hormones. Mesenchymal
stem cells committed to bone formation are
referred to as osteoprogenitor cells. These cells give
rise to pre-osteoblasts which differentiate into secretory
osteoblasts.
Osteoblasts synthesize and secrete type I collagen
and a number of noncollagenous proteins. The latter
include osteocalcin, which functions to limit bone
formation, and osteonectin, which appears to play a
role in the survival of bone cells. The osteoblasts also
secrete large quantities of alkaline phosphatase, providing
the inorganic phosphate component of bone.
Osteoblasts initiate bone resorption by producing proteases
which remove surface osteoid. The presence of
cell-surface receptors for most chemical mediators of
bone metabolism is evidence of the role of osteoblasts
in the regulation of bone turnover. A subpopulation of
osteoblasts, known as lining cells, lie as nonsynthesizing,
fl attened cells along trabecular surfaces.
Osteocytes
Calcifi cation induces morphological and metabolic
changes in the osteoblast, converting this bone cell
into an osteocyte. Osteocytes are surrounded by
newly synthesized bone matrix. They are mature bone
cells and have no mitotic potential or secretory activity.
In developing bone, their cytoplasmic processes
extend for considerable distances in narrow channels
called canaliculi and make contact with processes of
neighbouring osteocytes via gap junctions. The network
thus formed allows molecules to be passed from
cell to cell. In mature bone the processes are almost
completely withdrawn, but the canaliculi remain to
provide an avenue for the exchange of nutrients and
waste products between the blood and the imprisoned
osteocytes.
Osteoclasts
Osteoclasts are multinucleated giant cells that are
solely responsible for the resorption (destruction) of
bone matrix – both mineral and organic components.
Their progenitors are mononucleate haematopoietic
cells of the monocyte/macrophage lineage which,
when stimulated, fuse together to become mature
osteoclasts. Resorption is important in the development,
growth, maintenance and repair of bone. The
cells are found in or near cavities called Howship’s
lacunae on bone surfaces. Osteoclasts express on
their surfaces many receptors for calcitonin, which
is a potent inhibitor of the cell’s resorptive activity.
The surface of the osteoclast facing the bone matrix is
termed the ruffl ed border, owing to extensive infoldings.
Adjacent to the ruffl ed border in the cell’s interior
is a so-called clear zone that is rich in actin fi laments
but devoid of organelles. The clear zone is a site
of adhesion of the osteoclast to the bone matrix and
creates a microenvironment of low pH and lysosomal
enzymes for bone resorption. Osteoclasts secrete acid,
collagenase and other proteolytic enzymes that dissolve
the bone matrix. The ruffl ed border is essential
for the activity of the osteoclast. In osteopetrosis, a
genetic disease characterized by dense heavy bone,
the osteocytes lack ruffl ed borders and bone resorption
is defective.

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