Biomedical Engineering Reference
In-Depth Information
Table 8.1.
Major proteins associated with the osteoblast phenotype
Protein
Function [reference]
Type I collagen
Provides the organic matrix for mineralization
Alkaline phosphatase
Marker for osteoblast differentiation; thought to be critical for regulating Pi/PPi and
subsequently biomineralization [51]
Osteopontin (OPN)
Present in many tissues, with high concentration in bone. Various roles assigned to
OPN include regulation of crystal growth, protection against cell death, regulation of
inflammation, and promotion of osteoclast adhesion [12]
Osteocalcin
A late marker of the osteoblast phenotype. A modulator of crystal growth [26, 126]
Osteonectin/SPARC
Found in many tissues. In bone, rises during the increased mineralization
(reparative) phase; may mediate deposition of hydroxyapatite; considered to have a
role in angiogenesis [80]
Bone sialoprotein
Thought to enhance mineralization and support osteoblast cell attachment [9, 35,
56, 66]
Wnts
Bind to their receptors and then regulate LEF1/TCF; promote osteoblast maturation
and may play a role in lineage commitment of mesenchymal precursor cells [87, 114,
125]
Transforming growth factor
β
Regulate a myriad of cellular processes based on their extracellular concentration.
(TGF-
β
) superfamily (bone
At low concentrations, promote chemotaxis and cellular proliferation; at high
morphogentic proteins, BMPs)
concentrations, facilitate cellular differentiation and bone formation (e.g., BMP-2, -4,
-7) [115, 116, 127]
Parathyroid hormone-related
Proven to act in many tissues to regulate both development and function; inhibits
peptide (PTHrP)
bone resorption; thought to be a signaling molecule in epithelial-mesenchymal
interactions [11, 49, 122]
Fibroblast growth factors (FGFs)
Modulate cell migration, angiogenesis, bone development and repair, and
epithelial-mesenchymal interactions; e.g., FGF-2 stimulates osteoblast proliferation
and enhances bone formation [42, 83, 89, 90]
Healing in craniofacial bone, ileum, scapula,
and clavicle mainly involves intramembranous
bone formation. Some examples of factors and
proteins that affect the differentiation of MSCs
into cartilage and bone during postnatal bone
growth include Indian hedgehog (
ihh
), BMPs,
Wnts, Sox, parathyroid hormone-related
peptide (PTHrP), and transcription factor
gli3
(Table
Numerous factors, including macrophage
colony-stimulating factor (M-CSF), tumor
necrosis factor
α
(TNF-
α
), receptor activator
of nuclear factor
B (RANK) and its ligand
RANKL, and osteoprotegerin (OPG) [
κ
], have
been shown to play critical roles in balancing
osteoblast-osteoclast homeostasis. M-CSF
promotes osteoclast maturation, whereas
RANKL is required for activating the osteoclast
to resorb bone. RANK, which is expressed
by osteoclast progenitors and mature osteo-
clasts, binds to its ligand, RANKL, which is
expressed on osteoblasts and stromal cells. For
example, osteoblasts activated by signaling
factors such as parathyroid hormone (PTH)
and lipopolysaccharide (LPS) enhance their
secretion of OPG and/or RANKL. RANKL
binds to RANK receptors and activates
osteoclasts, whereas OPG acts as a delay and
blocks RANKL-RANK-mediated osteoclast
activation. When osteoclasts become stimu-
lated, they home to osteoblast-vacant zones,
attach at these sites, and resorb mineralized
tissues.
72
). During this stage, collagen fi bers
are not perfectly aligned, and as a result a loose,
unorganized woven tissue is produced.
8
.
2
8.2.1.3 Remodeling Phase
After primary formation, healing skeletal tissue
reaches phase
, the remodeling phase. In this
phase, the unorganized bone woven produced
in phase
3
is replaced with a more organized
structure, signaling the complete restoration of
damaged bone. The remodeling process, known
as activation-resorption-formation (ARF), is
guided by expression of specifi c genes and
associated proteins, protein synthesis and
secretion, and physical activity.
2
