The main structure of the skeletal system is composed of
cartilage and bone. Both are connective tissues, that is, they are made of
cells which are embedded in the matrix with intracellular fibres. They form the
essential structural component of the body. Cartilage and bone are different in
their composition and function. Cartilage is a semi-rigid connective tissue
therefore it does not contain the hard properties of bone, it is very flexible.
The mature cartilage is avascular meaning it contains no blood vessels, this
makes healing process difficult and long. Nutrients required for the cartilage
are diffused through the matrix. Due to its flexibility, cartilage supports
soft tissue such as the airway of the respiratory system or the auricle of the
ear. It has also been identified in the meniscus of the knee, the nose and
pubic bone. Bone is the most rigid of the connective tissue, its extracellular
matrix is rigid. It is strengthened through the process of calcification,
minerals which have been deposited in the matrix, and is the main store and
source of calcium phosphate. The function of bone includes supporting the body
by aiding in movement and hemopoiesis. Dysfunction of bone and cartilage can
consequently lead to Osteoarthritis and Osteomalacia.

The initial formation of cartilage requires the condensation
of chondroblasts into chondrocytes. Chondroblasts are mesenchymal progenitor
cells which are important in chondrogenesis due to their ability to
differentiate into chondrocytes and form extracellular matrix which together
will form the cartilage. They also produce extracellular matrix components such
as proteoglycan and collagen fibres. Chondrocytes are the mature cartilage
cells, they are embedded in the cartilage matrix and trapped in a structure
called the lacunae, and the number of chondrocytes in lacunae determines how
flexible the cartilage is. The role of chondrocytes is for the production and
maintenance of the cartilage matrix.

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There are three types of cartilage, this includes elastic
cartilage, hyaline cartilage and fibrocartilage.

cartilage contains threadlike structures which makes up the elastic fibres
inside the extracellular matrix. Associated with the elastic fibres are
chondrocytes which are in lacunae. Perichondrium surrounds the surface of the
cartilage, it contains blood vessels and nerves which is essential for the
development of new cartilage. Elastic cartilage is located on areas such as the
trachea, true vocal cords, and ligaments of the penis and lung tissue. Their
function is to allow the stretching of some organs such as those of the lungs
which recoils when exhaling. It ensures that after being stretched, they recoil
to their original shape (Tortora, 2011).

Hyaline cartilage contains fine collagen
fibres which are not visible when using ordinary staining technique. They also
contain chondrocytes in lacunae with their surface surrounded by periosteum.
Hyaline cartilage has a resilient gel as ground substance and are blue-white
shiny substance in the body. It is mainly located at the end of long bones,
fetal skeleton and part of the larynx. They enable smooth movement of joints
preventing them from grinding together. These are the most common type of
cartilage in the body however, they are also the weakest. Hyaline cartilage in
joints are referred to as articular cartilage (Tortora, 2011).

The structure
of fibrocartilage consists of thick visible collagen fibres    in ground substance within the extracellular
matrix. They also contain chondrocytes in lacunae however, they do not have
periosteum. They are in intervertebral discs and pubic symphysis. Their role
involves supporting and joining different structures together. These are the
strongest of the cartilage because they contain less chondrocyte therefore are
more rigid (Tortora, 2011).

The growth of cartilage involves either interstitial growth
or appositional growth. Interstitial growth occurs within the tissue by the
increase in size because of the division of chondrocytes and increase
production of extracellular matrix from inside the lacunae. The increase amount
of the matrix further separates the chondrocytes from each other, expanding the
cartilage from within. Division of chondrocytes is by mitosis, producing two
chondrocytes per lacunae. This increases the cartilage in width. Appositional
growth occurs along the outside edge of the cartilage. There are stem cells in
the perichondrium which undergoes mitosis to produce chondroblasts, these are
added to the periphery producing matrix and differentiating into chondrocytes
which forms new lacunae.  The lacunae are
added to an existing matrix leading to the formation of a larger piece of
cartilage. Appositional growth increases the cartilage in length and s used for
endochondral bone formation.

Adult human has a total of 213 bones in their body (Clarke, 2008).
These bones undergo modelling for replacement of old or damaged bone. Bones are
separated into four categories which are long bones, short bones, flat bones
and irregular bones.

bones include the femur and clavicles, they are a result of endochondral and
membranous bone formation. Long bones are made of the diaphysis, epiphysis and
metaphysis. The epiphysis is the ending of bone, it forms a rounded region at
the end and strengthens the joints. It also acts as an attachment site for tendons
and ligaments. Where the long bone may meet another contains a thin layer of
articular cartilage, reducing friction. The metaphysis is between the epiphysis
and diaphysis, it contains epiphyseal which is a growth plate that allows the
bones to grow longer. It is made from hyaline cartilage. The diaphysis is made
from mainly compact bone whereas epiphysis and metaphysis are made of spongy
bone (Clarke, 2008).

On the outside of the bone is dense irregular connective
tissue, periosteum. They contain two layer, the inner cellular and vascular
layer allows for the formation of new bone whereas the outer fibrous layer aids
in insertion of ligaments, tendons and muscles (Buckwalter and Cooper, 1987). It acts as an anchor for blood
vessels and nerves and is held firmly to the bones by perforating fibres embedded
in the bone matrix. Stem cells are found in the periosteum, they migrate
allowing the growth of bone and healing properties. The spongy bone contains
the periosteum but not endosteum. Endosteum lines the inside of the bone marrow
cavity, however small cavities on the spongy bone is lined with endosteum. The
bone matrix consists of organic components such as bone cells, collagen fibres
and ground substances. Also, inorganic substances such as bone salt crystals,
hydroxyapatite, which hardens the ground substance and calcium phosphate and


There are two types of bone tissue, compact bone and spongy
bone. Flat bones contains both spongy and compact bones, they are found at the

compact bone makes the exterior of the flat bone and the shaft of the long
bone. Compact bone and spongy bone consists of osteons, also known as the
Haversian system, they are cylindrical and form branched network within the
cortical bone. Compact bone consists of an outer periosteal surface, which is
essential for appositional growth and repair. It also consists of an inner
endosteal surface.  The spongy bone also
contains osteons called packets. They are semilunar and made of concentric
lamellae (Clarke, 2008).

The bone has four different types of cell, these are
osteoprogenitor cells, osteoblasts, osteocytes and osteoclast. Osteoproginitor
cells are stem cells which are located at the periosteum and endosteum, the
role is to produce more stem cells or osteoblasts.

Osteoblast are located at the surface of the bone, they are
required for the formation of bone. Osteoblast is characterized by the presence
of protein synthesising cell which includes rough endoplasmic reticulum and the
Golgi apparatus. They produce the unmineralized organic component of bone
(osteoid) toward the matrix of the bone. Osteoblast are derived from mesenchymal
stem cells, this process requires the expression of specific genes. This
includes the pathway of bone morphological protein (BMPs) and members of the
wingless (Wnt). Osteoblast differentiation is regulated by expression of
Runt-related transcriptional factors 2, Distal-less homeobox 5 and osterix
(osx). Osteoblast progenitor shows alkaline phosphate activity, this makes
pre-osteoblast which are differentiated to osteoblast by the increase
expression of osx and formation of bone matrix proteins, collagen I and
osteocalcin (Florencio-Silva et al., 2015).

Osteocytes are derived from osteoblasts, they are located in
lacunae which are surrounded by mineralized bone matrix. Osteocytes in spongy
bone are round whereas in compact bone are more elongated. They are required
for the maintenance of the strength of bones. Osteocytes derived osteoblast
involves protein E11/gp38. It is shown to be highly expressed in embedded

Osteoclast is a multinucleated bone cell, its function
involves absorbing bone tissue during growth and repair. They are made from
hematopoietic stem cell which are stimulated by macrophage colony-stimulating
factor and RANK ligand. These two factors are responsible for gene expression
in osteoclast. The binding of M-CSF and RANKL to its receptor in osteoclast
precursor stimulates its proliferation, also inhibiting apoptosis (Florencio-Silva et al., 2015).

Bone formation: intramembranous ossification and endrochondral

Intramembranous ossification involves the differentiation and
condensation of mesenchymal stem cell into compact nodule. Numerous cells
undergo changes to become osteoblast which then secretes a
collagen-proteoglycan matrix containing calcified salt. As a result, the pre-bone
is calcified. Osteoblasts are trapped in the calcified matric, becoming
osteocytes. Continuous calcification leads to the removal of bony spicules away
from the initial ossification site. Calcified spicules are surrounded by
compact mesenchymal cells (MS) forming the periosteum. The process of
intramembranous ossification requires bone morphogenetic protein (BMPs) and
activation of transcription factor (CBFA1). BMPs sends instructions for MS to
become bone, it activates the Cbfa1 gene in the cells which transforms MS into
osteoblast (Gilbert, 2000).


Endrochondral ossification involves the formation of
cartilage from mesenchymal stem cells, the cartilage is then used as a template
for bone formation. This process is divided into five stages. The first stage
involves the formation of the cartilage from the MSC, this is initiated by
paracrine factors which causes nearby mesodermal cells to express
transcriptional factors Pax1 and Scleraxis. These transcription factors
activate cartilage specific genes. The second stage involves the condensation
into compact nodules and later differentiation into chondrocytes which is the
cartilage cell. The initiation of condensation is performed by N-cadherin and
the maintenance of it requires N-CAM in mouse embryo, however SOX9 gene is
expressed in humans. In the third stage, proliferation of the chondrocytes
occurs for formation of model required for bone. When the chondrocytes divide,
they secrete extracellular matrix.   In
the fourth stage, the chondrocyte stop dividing and increase their volume
becoming hypertrophic. This allows mineralization of the matrix by calcium
carbonate. The fifth stage is the invasion of cartilage model by blood vessels
allowing the death of chondrocyte cells by apoptosis. The space left becomes
bone marrow and the death of cartilage cells lead to the formation of
osteoblast which forms the bone matrix until all the cartilage has been
replaced by bone. However, not all cartilage are calcified, there is a
cartilaginous area at the ends of long bone called epiphyseal growth plates which
contains “a region of chondrocyte proliferation, a region of mature
chondrocytes, and a region of hypertrophic chondrocyte” (Gilbert, 2000).

Osteomalacia is a metabolic disease from limited
mineralization of osteoid in mature compact and spongy bone. It involves the
inhibition of mineral calcification and deposition, therefore there is no
change in bone mass, and replaced bone consists of soft osteoid rather than a
rigid born. This is a result of vitamin D deficiency which decreases plasma
calcium concentration, leading to the activation of PTH which stimulates renal
clearance of phosphate. The decrease in phosphate in the bone inhibits
mineralization. In contrast, osteoarthritis is an age-related disorder
associated with the loss and damage of the articular cartilage, it is usually
located in the hips or hands. The exact cause still remains unclear however it
has been suggested that genetics, inflammation and metabolic factors play an
important role.  It involves a complex
interaction of transcriptional factors, cytokines and growth factors. Clinical
manifestation includes pain in the joints, stiffness, discolouration, muscle
wasting and deformity. In Osteomalacia, the individual may experience muscular
and skeletal pain, they are also more common in the hips. Muscular weakness may
lead to “a waddling gait”, facial deformities may be present and the bone of
the back can easily fracture with little effort (Huether and McCance, 2012).

The general principles of some treatment for Osteomalacia
are taking vitamin D supplements, bisphosphate, and chelation of bone aluminium
and adjustment of serum calcium and phosphorus level. For osteoarthritis, the
patient are examined using radiologic studies and clinical assessment, they are
encouraged to rest and use of crutches to prevent joint contraction. Injection
with hyaluronic acid reduces knee pain, however new investigation are made to
if agents such as leptin would work. Surgery can be used to place artificial

In conclusion, bone and cartilage are essential
for the development of the skeletal system, dysfunction with either of them may
lead to disorders such as Osteomalacia or osteoarthritis which can be life

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