Biomedical Engineering Reference
In-Depth Information
Table 8.2.
Transcription factors associated with bone metabolism
Factors
Functions [reference]
Runx2/Cbfa1
A runt domain containing transcription factor essential for
osteoblast and hypertrophic chondrocyte differentiation and bone
formation during embryogenesis and postnatal life [27, 76, 88]
Osterix (Osx; SP7)
Transcription factor containing a zinc-finger motif and essential
function for osteoblast differentiation; may prevent chondrocyte
differentiation [17, 40, 91]
ATF4 (CREB2; cAMP response-element
A basic leucine-zipper transcription factor and a member of the
binding protein 2)
ATF/CREB protein family. ATF4 is involved in regulation of
osteoblast differentiation and bone formation and exhibits
cooperative interactions with Runx2/Cbfa1 [123, 124]
NFAT (nuclear factor of activated T cells)
NFAT forms a complex with osterix that binds to DNA. This
interaction appears to be important for the transcriptional activity
of osterix [73]
β
-Catenin/TCF/LEF (TCF, T-cell factor;
Transcription regulatory DNA binding complex considered to play
LEF, lymphoid enhancer factor)
multiple critical roles in osteoblast differentiation [10, 41, 48]
Osteoclast transcription factors: PU.1; Fos/Fra1;
Several transcription factors are involved in promoting osteoclast
NFATc1 (nuclear factor of activated T cells,
differentiation and maturation from hematopoietic lineage cells.
cytoplasmic, calcineurin-dependent 1); NF
κ
B
A few such factors are listed here [72]
(nuclear factor
κ
B); MITFs (microphthalmia-
associated transcription factors)
This is a very limited list of some of the key transcription factors associated with bone tissues. For more details, please refer to the
references cited in the table and Bilezekian et al. [4]
Following activation, lysosomal enzymes,
such as tartrate-resistant acid phosphatase
(TRAP) and cathepsin K, are synthesized and
secreted through the ruffl ed border into the
extracellular bone-resorbing compartment of
woven bone. The osteoclast also secretes
various metalloproteinases, including collage-
nases. These enzymes dissolve and degrade the
bone mineral and organic matrix. Resorption
of woven bone releases noncollagenous pro-
teins, such as BMP and TGF-
cells (osteoblast, osteoclast, and osteocyte)
responsible for the ARF process is called the
basic multicellular unit
(BMU) [
36
]. In humans,
the ARF takes approximately
months to
complete a remodeling cycle, and the events
continue throughout adult life. Changes in
estrogen levels, such as those occurring in
postmenopausal women, can alter bone homeo-
stasis; hence the increased susceptibility of
women in comparison with men to bone frac-
tures with age. This dynamic remodeling
process generates microstructures, including
lamellae, haversian canals, and the defi ned ori-
entations of mature trabecular bone.
3
to
6
, which are
thought to stimulate osteoblastic activity. In
response to an as yet unidentifi ed signal, osteo-
clasts cease resorbing and abandon their
attachment to bone [
β
]. Osteoclastic resorp-
tive pits (Howship's lacunae) are repopulated
by osteoblasts to produce osteoid, which then
mineralizes to restore bone.
It is now recognized that osteocytes, in addi-
tion to osteoblasts and osteoclasts, play an
important role in remodeling [
52
8.2.2 Mechanical Effects on
Bone Healing
A century ago, Wolff [
] studied biomechan-
ics using the femur and discovered that the
orientation of trabecular bone coincided with
stress patterns. This discovery came to be
called Wolff's law: bony architecture aligns
with the direction of principal stresses. Since
that time, researchers have worked diligently to
121
]. Osteocytes
can be modulated by environmental factors
such as fl uid fl ow. Mechanical deformation of
osteocytes alters gene expression and leads to
secretion of biochemical signals that regulate
osteoblast and osteoclast activity. The group of
7
