Clinical and Technical Review - Tecomedical

4
Bone Formation
Osteoblast:
The osteoblast is the bone cell responsible for:
1) The formation and organization of the extracellular matrix
(ECM) of bone and its subsequent mineralization;
2) Synthesis of collagen and other bone proteins. Three
periods are distinguished in the osteoblast life cycle.
A) Cell proliferation: genes associated with formation of the
ECM, like Type I Collagen, are expressed and gradually
down regulated.
B) ECM maturation: proteins associated with the osteoblast
phenotype are expressed, like Bone-specific Alkaline
Phosphatase (BAP).
C) ECM mineralization: BAP gene expression declines,
Bone Sialo Protein (BSP), osteopontin and osteocalcin
gene expression increase.
Bone matrix:
Consists of Type 1 collagen (90 % of the protein in bone),
osteocalcin, osteopontin, osteonectin, proteoglycans,
alkaline phosphatase and bone sialo protein.
Proteins
OPG:
OPG (Osteoprotegerin) or OCIF (Osteoclast Inhibiting
Factor) or OBF (Osteoclast Binding Factor) is a key factor in
inhibition of osteoclast differentiation and activity.
It binds and acts as as decoy receptor for s-RANKL.
sRANKL:
Soluble Receptor Activator of Nuclear factor (NF)-κB Ligand.
sRANKL binds to osteoclast receptor: RANK (NF-κB ) and is
the main stimulatory factor for the formation of mature
osteoclasts.
BAP:
Bone-specific Alkaline Phosphatase is an osteoblastic enzyme
involved in bone formation. It is assumed that BAP plays
a role in ECM maturation. BAP is a key biochemical bone
marker used for assessing bone turnover and
monitoring therapy.
Bone Sialoprotein (BSP):
Major structural protein of the bone matrix, expression of
BSP is normally restricted to mineralized connective tissues
of bones and teeth. This role has been associated with
mineral crystal formation.
Osteocalcin:
Major structural protein of the bone matrix, binds calcium
and attracts osteoclasts.
Osteonectin:
Protein that binds calcium and is involved in regulation
of mineralization.
Osteopontin:
Cell-binding protein that anchors osteoclasts to
mineralised matrix.
Proteoglycans:
Monomer looks like test tube brush with keratan and
chondroitin sulphate chains (= GAGs) bound to a protein
core molecule. Monomers are attached via a link protein
to hyaluronic acid.
DKK-1:
Dickkopf-1(DKK-1) is a 28,672 Da secreted protein that acts
as soluble inhibitor of the WNT signalling pathway. DKK-1
regulates different developmental processes and is also
involved in the regulation of bone metabolism as it inhibits
the differentiation of osteoblast.
Collagen metabolites and epitopes
Type I Procollagen:
Secreted precursor of Type I Collagen. Extracellular cleavage
results in N- and C-terminal propeptides.
PINP:
Epitope of N- terminal propeptide, released during cleavage
of Type I Procollagen.
CICP/PICP:
Epitope of C- terminal propeptide, released during cleavage
of Type I Procollagen (PICP = CICP).
Type I Collagen:
Collagen molecules consist of three chains to form a triple
helix. Crosslinks between the chains and the molecules of
collagen give collagen its strength.