Biomedical Engineering Reference
In-Depth Information
phenotype requires the expression of Runx2, osterix (Osx), and several
components of the Wnt signaling pathway.
78, 82-84
The mature osteoblast
expresses the matrix proteins type I collagen (col I) and osteocalcin (Oc)
and a key enzyme in the mineralization process, alkaline phosphatase (alk
Phos), as a row of active osteoblasts secretes unmineralized matrix (osteoid).
These cells will either become bone lining cells or become incorporated
into the bone matrix. Those cells that become incorporated into the matrix
will gradually develop long cytoplasmic processes in order to remain in
communication with surrounding cells and upregulate expression of e11,
an early osteocyte marker.
85
at this point the cells are considered immature
osteocytes. as the matrix matures and mineralizes, and the osteoid seam
moves further away, the osteocyte becomes entombed in a bony matrix and
begins to mature and express a new set of genes, including dentin matrix
protein-1 (dMP-1), matrix extracellular phosphoglycoprotein (MePe) and
sost.
86-90
Osteocytes are the most numerous cells in bone and are found dispersed
throughout the matrix where they occupy lacunae (Fig. 2.3B,c). Lacunae
are interconnected by an elaborate network of thin tunnels called canaliculi
through which osteocytes pass cytoplasmic or dendritic processes.
91
These
processes connect individual osteocytes with neighboring cells via gap
junctions to facilitate both the transport of nutrients for osteocyte viability and
the conveyance of intercellular messages.
92, 93
Intercellular communication
is also facilitated by the osteocytic release of signaling molecules into the
extracellular fluid which flows through the lacuna-canalicular system.
94, 95
Osteocyte function remains unclear; however, their principal role appears to
be the sensing of mechanical stimuli. Osteocytes have long been considered
the mechanosensor in bone because of their sheer numbers, distribution and
interconnectivity.
96
It is only recently that supportive data has been generated
to implicate the osteocyte network as the primary mechanosensory cell
type, to the exclusion of other bone cells.
97, 98
This evidence is discussed in
greater detail later in this chapter. In addition to mechanosensation, recent
evidence has also found osteocytes to have the capacity to regulate mineral
metabolism and alter the properties of their surrounding matrix.
98-100
2.4 Bone physiology
Bone is a dynamic tissue capable of altering its structure and mass in order
to adapt to changing requirements. This is achieved via a number of different
fundamental tissue-level activities, including repair, growth, modeling and
remodeling.
101, 102
It is suggested that each of these activities have their
own functions, mediator mechanisms and responses to drugs, hormones,
mechanics and other agents.
101, 102
Bone growth, modeling and remodeling
will be discussed below.
