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Growth plate calcification
Growth plate
The growth plate is a highly specialised mesoderm derived hyaline cartilaginous structure
situated between the epiphysis and metaphysis of growing bones
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The
growth plate is a multilayered structure composed of the resting zone, the proliferative zone,
the transformation zone, and the degeneration zone
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The number of reserve zone cells determines the longevity
of the growth plate
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In the
transformation zone, cells undergo terminal differentiation and prepare for rapid increase in
size
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in the hypertrophic zone, chondrocytes rapidly increase in cell cytoplasmic
volume
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In
the degeneration zone, cells undergo chondromatosis, ie
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Calcification of the growth plate
The plasma protein fetuin-A/alpha2-HS-glycoprotein is an inhibitor of excessive
mineralisation in the growth plate cartilage matrix, as evidenced in knockout murine
experiments
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The concentrations within the extracellular matrix of the
C-propeptide of type II collagen, aggregating proteoglycan, and hypertrophic zones, being
maximal at the time of mineralisation
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This is associated with the unwinding of the triple helix of type II collagen
which starts in the pericellular sites in the zone of maturation, when type X collagen is first
synthesized, and then extends throughout the hypertrophic zone
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Aortic
valve calcification can sometimes be seen on chest radiography, and the presence of such
calcifications is a sensitive marker for clinically significant aortic stenosis
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Examples of vascular calcification include; vascular
mammary calcification
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Vascular calcification is associated
with an increased risk of; amputation due to damage to vasculature and consequent poor
perfusion of tissues resulting in necrosis of cells thus necessitating amputation, ischaemic

heart disease as a result of calcification occuring in blood vessels surrounding the heart,
storke, and mortality
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Vascular structure; tunica intima, the
innermost layer composed of endothelial cells lining the vesicle lumen; tunica media, the
middle layer composed of smooth muscle cells and elastic fibres which allow for constriction
of blood vessels to control blood flow; and tunica adventitia, the outermost layer composed
of collagen fibres which maintain structural integrity of the vessel
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Calcification can occur in
the tunica media of peripheral arteries and is known as Monckeberg’s sclerosis and occurs
mainly in older, diabetic patients
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The initial step in calcification of the tunica intima is the accumulation of lipid rich
macrophages and T-lymphocytes in the vessel wall forming fatty streaks, followed by
invasion of vascular smooth muscle cells (VSMCs)
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VSMCs then proliferate and initiate
synthesis of the extracellular matrix (ECM)
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Evidence linking VSMCs, the growth plate, and calcification
In vivo evidence suggests VSMCs are directly involved in the process of calcification
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VSMCs may differentiate into chondrocytes
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Given this evidence, pathological calcification may share
many molecular and cellular features with bone cartilage mineralisation which occurs in the
growth plate, and VSMCs share similarities with cells present in the growth plate
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SOX9 positively regulates the synthesis of collagen II,
IX, and X, which are required for mineralisation
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RUNX2 induces production of collagen type X which is deposited into the matrix
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When VSMCs are grown in culture they express SOX9 and RUNX2 which are markers for
chondrocyte differentiation
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Type X collagen has been identified in coronary calcification in a rat model
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Transcription factors which drive differentiation are shared between cells of the growth plate
and VSMCs in the tunica intima of vesicles with pathological calcification
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The size of ECM vesicles ranges from
30-1000 nm, requiring an electron microscope for visualisation
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ALP squesteres calcium and phosphate in vesicles,
thus when bone forms there is a store of calcium and phosphate for the mineralisation
process
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The size of VSMC matrix vesicles ranges from 100-700 nm, and thus are similar in size to
growth plate vesicles
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The first crystals of appetite bone mineral are formed within matrix vesicles close to the inner
surfaces of their investing membranes
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Polarized release of matrix vesicles
into selected areas of the developing matrix determines the nonrandom distribution of
calcification
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Phase 2 of biologic mineralisation begins with crustal release through
matrix vesicle membrane, exposing preformed hydroxyapatite crystals to the extracellular
fluid
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In diseases such as osteoarthritis, crystal
deposition arthritis, and atherosclerosis, matrix vesicles initiate pathologic calcification, which
in turn, arguments disease progression
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Apoptotic bodies, if not cleared, may classify
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VSMC remnats and
apoptotic odies are present in atheroscleortic plaques

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