Bone osteo? calcin and alkaline phosphatase, which is essential

Bone Remodeling:

Bone is a rigid body tissue consisting of cells
embedded in an abundant, hard intercellular material. The two principal
components of this material is collagen and calcium
phosphate. Bone may seem to be stable and unchanging, but in fact, bone is
constantly being remodeled. Bone
remodeling is a continuing process of synthesis and destruction that
gives bone its mature structure and maintains normal calcium levels in the
body. While the osteoclasts resorb bone at various sites, the other cells
called osteoblasts make new bone to maintain the skeletal
structure. During childhood, bone formation outpaces destruction as growth proceeds. After
skeletal maturity is reached, the two processes maintain an approximate
balance. When the coupling is lost, the correct bone mass could be
compromised, leading to several skeletal pathologies.

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Cells involved in the bone remodeling:

Osteogenic Cells:

Osteogenic cells or Osteoprogenitor cells are
derived from primitive mesenchymal stem cells (MSCs). They are the only cells
of bone that are capable of differentiate or divide and develop into osteoblast
or chondrocytes depending on the signaling molecule. Immature osteogenic cells
are found in the deep layers of the periosteum and the marrow. In
mature bone in which there is no active new bone formation or remodelling,
the osteoprogenitor cells become
flattened spindle cells closely applied to the bone surface, when they are
sometimes called ‘inactive osteoblasts’. In actively growing bone, however, for
example in fetal bone or in a period of high turnover in adult bone, these
cells are much larger and more numerous, containing plump oval nuclei and more
abundant spindle-shaped cytoplasm.

 

Osteoblast:

Osteoblasts derive from mesenchymal precursor cells, which
also originate, chondrocytes (cartilage), adipocytes (bone marrow stroma),
fibroblasts (periosteum), and adventitial reticular cells (bone marrow stroma).
The osteoblast resides along the bone surface at sites of active bone
formation. They secrete type 1 collagen, the basic building block of bone;
non-collagenous proteins including osteo? calcin and alkaline phosphatase,
which is essential for mineral deposition. Osteoblasts work as a group to form
new bone. The principal function of the osteoblast is bone formation and these
occur via two distinct mechanisms: the intramembranous ossification (flat bones
of the skull and most of the clavicle) and the endo? chondral ossification,
which produces most bones, involves the transformation of mesenchyme 2 Topics
in Osteoporosis into a cartilage model that resembles the shape of the bone
8. They are also responsible for the mineralization, although the exact
mechanism by which mineralization occurs remains unclear 9. Mature
osteoblasts have one of three fates: they undergo apoptosis, differentiate
further into osteocytes or become quiescent lining cells. Approximately 50 to
70% of osteoblasts undergo apoptosis.

Osteocytes:

Osteocytes
are non-proliferative, terminally differentiated cells of the osteoblast
lineage. They reside both in the mineralized bone matrix and in newly formed
osteoid. They are the primary cell of
mature bone and the most common type of bone cell but smaller than
osteoblasts. Each osteocyte is located in
a space (lacuna) surrounded by bone tissue. Osteocytes maintain the mineral
concentration of the matrix via the secretion of enzymes. They compose over 90–95%
of all bone cells in the adult skeleton. In absence of major cells they are thought
to respond to mechanical strain to send signals of resorption or formation
because of their distribution throughout the bone matrix and extensive
interconnectivity. Evidence suggests that the primary function of the osteocyte
relates to the determination and maintenance of bone structure.

 

Osteoclast:

Bone is a dynamic tissue that is
continuously being broken down and restructured in response to such influences
as structural stress and the body’s requirement for calcium. Osteoclasts, multinucleated monocyte-macrophage derivatives are the mediators of the continuous destruction of
bone. They are the giant cell formed through fusion of a number of osteoclast
precursor cells in a process termed osteoclastogenesis. The cell is attached to a spicule of bone which is
it degrading these cells have distinct morphological and phenotypic
characteristics that are routinely used to identify them, including expression
of tartrate-resistant acid phosphatase and the calcitonin receptor.Osteoclast differentiation is supported by cells of the
osteoblast lineage that express membrane-bound receptor activator (RANK) of
RANKL (NF-kB ligand) and macrophagecolony stimulating factor (M-CSF) ; this
process is also regulated by a secreted decoy receptor of RANKL,
osteoprotegerin (OPG), which functions as a paracrine inhibitor of osteoclast
formation.

Bone lining cells:

The
bone lining cells constitute a subpopulation of the osteoblast family. Bone
lining cells were characterized by their long, slender, and flattened appearance. They associated  with the bone surface at sites where a thin no
mineralized collagen layer was present. The bone lining cells contained a low
level of labeled osteocalcin, and they have electron-dense vacuoles containing
crossbanded collagen fibrils in the cytoplasm.
It has been proposed that bone lining cells play a role in bone remodeling by
preventing the inappropriate interaction of osteoclast precursors with the bone
surface. It is thought that the signals that initiate osteoclast formation may
stimulate the bone lining cells to prepare for bone resorption.

 

The bone remodelling
process:

Bone remodeling is accomplished according to the following
phases-

Activation phase:

 

 

 Different inputs, such as a
micro-fracture, an alteration of mechanical loading sensed by the osteocytes or
some factors released in the bone microenvironment, including insulin growth
factor-I (IGFI), tumour necrosis factor-a (TNF-a), parathyroid hormone (PTH)
and interleukin-6 (IL-6), activate the lining cells which are quiescent
osteoblasts. As a consequence, lining cells, increase their own surface expression
of RANKL (Receptor Activator of Nuclear kB Ligand), which in turn interacts
with its receptor RANK (Receptor Activator of Nuclear kB), expressed by
pre-osteoclasts. RANKL/ RANK interaction triggers pre-osteoclasts fusion and
differentiation toward multinucleated osteoclasts. Resorption phase:

Once differentiated, osteoclasts polarize, adhere to the
bone surface and begin to dissolve bone. This function requires two steps: i)
acidification of the bone matrix to dissolve the inorganic component, and ii)
release of lysosomial enzymes, such as cathepins K, and of MMP9, both in charge
for the degradation of the organic component of bone. Once accomplished their
function, osteoclasts undergo to apoptosis. This is a physiological consequence
needed to avoid an excessive bone resorption.Reverse phase:

 The role of reverse cells has not been
yet completely clarified.  During Reversal phase the resorbed surface is prepared
for the subsequent Formation phase. A sugar-rich cement line is produced to
help bonding old bone and new bone. It is known that they are
macrophage-like cells with a likely function of removal of debris produced
during matrix degradation.Formation phase:

Bone matrix resorption leads to the release of several
growth factors herein stored, including bone morphogenetic proteins (BMPs),
fibroblast growth factors (FGFs) and transforming growth factor b (TGF b),
which are likely responsible for the recruitment of the osteoblasts in the
reabsorbed area. Once recruited, osteoblasts produce the new bone matrix,
initially not calcified (osteoid) and then they promote its mineralization,
thus completing the bone remodeling process.

Unbalance between the resorption and formation phases mirror
an incorrect bone remodeling, which in turn affects the bone mass, eventually
leading to a pathological condition.

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