UNIT 4: MECHANISMS OF

SUPPORT AND MOVEMENT

Functions of the skeletal system
The skeletal system is the body system composed of bones,
cartilages, ligaments and other tissues that perform essential
functions for the human body.

• Bone tissue, or osseous tissue, is a hard, dense connective

tissue that forms most of the adult skeleton, the internal
support structure of the body.
• In the areas of the skeleton where whole bones move against
each other (for example, joints like the shoulder or between
the bones of the spine), cartilages, a semi-rigid form of
connective tissue, provide flexibility and smooth surfaces for
movement.
• Additionally, ligaments are the dense connective tissue that
connect bones to other bones, tying skeletal elements
together
Support, Movement, and Protection

• Just as the steel beams of a building provide a scaffold to

support its weight, the bones and cartilages of the skeletal
system compose the scaffold that supports the rest of the
body. Without the skeletal system, it would be a limp mass of
organs, muscle, and skin.

• Bones facilitate movement by serving as points of attachment

for the muscles.

• Bones also protect internal organs from injury by covering or

surrounding them. Ribs protect lungs and heart, the bones of
the vertebral column (spine) protect the spinal cord, and the
bones of the cranium (skull) protect the brain.
Mineral and Fat Storage, Blood Cell Formation

On a metabolic level, bone tissue performs several critical

functions;

The bone tissue acts as a reservoir for a number of minerals

important to the functioning of the body, especially calcium,
and phosphorus.

These minerals, incorporated into bone tissue, can be released

back into the bloodstream to maintain levels needed to support
physiological processes.
Calcium ions, for example, are essential for muscle
contractions and are involved in the transmission of nerve
impulses.
Mineral and Fat Storage, Blood Cell Formation

Bones also serve as a site for fat storage and blood cell
production. The unique connective tissue that fills the interior
of most bones is referred to as bone marrow.
There are two types of bone marrow: yellow bone marrow and
red bone marrow.
1. Yellow bone marrow contains adipose tissue, and the
triglycerides stored in the adipocytes of this tissue can be
released to serve as a source of energy for other tissues of
the body.
2. Red bone marrow is where the production of blood cells
(named hematopoiesis, hemato- = “blood”, -poiesis = “to
make”) takes place. Red blood cells, white blood cells, and
platelets are all produced in the red bone marrow.
As we age, the distribution of red and yellow bone marrow
changes.
THE BONE TISSUE
• The adult human skeleton has a
total of 213 bones, excluding the
sesamoid bones.
• The appendicular skeleton has 126
bones, axial skeleton 74 bones,
and auditory ossicles six bones.
• Each bone constantly undergoes
modeling during life to help it
adapt to changing biomechanical
forces, as well as remodeling to
remove old, microdamaged bone
and replace.
• The adult human skeleton is
composed of 80% cortical bone
and 20% trabecular bone overall.
Different bones and skeletal sites
within bones have different ratios
of cortical to trabecular bone.
Define bone tissue
Bone is a mineralized
connective tissue that
exhibits four types of
cells: osteoblasts,
bone lining cells,
osteocytes, and
osteoclasts.
Bone is a composite
of organic and
inorganic phases.
Bone structure
Microfibrils of collagen, synthesized by osteoblasts, aggregate laterally
and longitudinally; forming fibres that are then called an osteoid.

The osteoblasts deposit HA crystals into the voids between the collagen
fibrils during a process called biomineralization.

The degree of biomineralization determines the mechanical properties of

the bone tissue; a higher degree of mineralized bone matrix provides a
stiffer structure, however, one that is more susceptible to fracture.
The long bones are composed of a hollow shaft, or diaphysis; flared,
cone-shaped metaphysis below the growth plates; and rounded
epiphysis above the growth plates.

The diaphysis is composed primarily of dense cortical bone, whereas

the metaphysis and epiphysis are composed of trabecular meshwork
bone surrounded by a relatively thin shell of dense cortical bone.

Cortical bone is dense and solid and surrounds the marrow space,
whereas trabecular bone is composed of a honeycomb-like network of
trabecular plates an d rods interspersed in the bone marrow
compartment.

Both cortical and trabecular bone are composed of osteons.

Categories of bone tissue

The four general categories of bones are long bones, short

bones, flat bones, and irregular bones.
Long bones include the clavicles, humeri, radii, ulnae,
metacarpals, femurs, tibiae, fibulae, metatarsals, and
phalanges.
Short bones include the carpal and tarsal bones, patellae, and
sesamoid bones.
Flat bones include the skull, mandible, scapulae, sternum, and
ribs.
Irregular bones include the vertebrae, sacrum, coccyx, and
hyoid bone.
 CELLS OF THE BONE TISSUE

Osteoprogenitor (Stem) Cells: Osteoprogenitor cells retain the ability

to re-differentiate into osteoblasts.

• They reside in the bone canals, endosteum, periosteum, and marrow.

They may regulate the influx and efflux of mineral ions into and out of
the bone extracellular matrix.

• They also are responsible for the formation of bone remodeling

compartments (BRC) with a specialized microenvironment.
 CELLS OF THE BONE TISSUE
Osteoblasts - Bone Forming Cells: They are tightly packed on the
surface of the bone.
• They synthesize and secrete bone matrix (osteoid). They also regulate
bone mineralization by secreting alkaline phosphatase (a marker for
bone formation) and a set of proteins known as dentin matrix protein
(DMP-1) and bone sialoprotein, which act as nucleators for
mineralization.
• Osteocalcin and osteonectin are calcium and phosphate binding
proteins secreted by osteoblasts, which regulate the deposition of
mineral by regulating the number of hydroxyapatite crystals.
Osteoblasts have 2 fates; (1) remain quiescent osteoblasts lining cells
or (2) become osteocytes.
• Osteoblasts regulate osteoclastogenesis and osteocyte formation.
Vitamin D and parathyroid hormone (PTH) stimulate osteoblasts to
secrete M-CSF and to express RANKL, which are important for
osteoclastogenesis.
 CELLS OF THE BONE TISSUE

Osteocytes - Mechanosensing Cells: These account for 90%

of all bone cells. They are derived from osteoblasts.
• They reside within the bone network known as the lacuna
canalicular system.
• They do not normally express alkaline phosphatase but
do express osteocalcin and other bone matrix proteins.
• They maintain a connection with each other and bone
surfaces via their cytoplasmic processes.
Osteocytes - Mechanosensing Cells: These account for 90% of all bone
cells. They are derived from osteoblasts.
• Osteocytes are linked metabolically and electrically through
gap junctions. Their primary function is mechanosensation.
• Osteocytes detect mechanical loading through physical
deformation of bone matrix and fluid flow shear stress
resulting from the flow of canalicular fluid through the
lacuna canalicular network.
• Osteocytes act as orchestrators of bone remodeling and as a
result, are also considered endocrine cells. They secrete
fibroblast growth factor (FGF23) to regulate serum
phosphate levels.
• FGF23 decreases renal and intestinal sodium and phosphate
co-transporter expression and subsequently increases renal
phosphate excretion by both kidneys.
 CELLS OF THE BONE TISSUE
Osteoclasts - Bone Resorbing Cells: These are multinucleated cells that
originated from mononuclear monocyte-macrophage cells.
• RANKL and M-CSF are two cytokines that are critical for osteoclast
formation. They are important for osteoclast precursors to proliferate
and differentiate into mature osteoclasts.
• Osteoprotegerin (OPG) is a membrane-bound secreted protein that
binds OPGL/RANKL to inhibit its action at the RANK receptor and
subsequently inhibit osteoclastogenesis.
• Bone resorption depends on osteoclast secretion of hydrogen ions,
tartrate-resistant acid phosphatase (TRAP), and cathepsin K enzymes.
Hydrogen ions acidify the resorption compartment beneath osteoclasts
to dissolve the mineral component of the bone matrix, whereas
cathepsin K and TRAP digest the proteinaceous matrix, which is mostly
composed of type I collagen.
• PTH stimulates osteoclast activity while calcitonin inhibits it.
Bone Extracellular Matrix
This makes up 90% of overall bone volume. It consists of
inorganic (mineral) and organic matrices.

a) Inorganic Bone Matrix: accounts for 99% of the body storage of

calcium, 85% of the phosphorus, and 40 to 60% of the magnesium,
and sodium. It is mainly in the form of hydroxyapatite
[Ca10(PO4)6(OH)2] to provide the bone its strength, stiffness, and
resistance to compressive forces.

b) Organic Bone Matrix: is secreted by osteoblasts and is predominantly

type I collagen. It also contains glycoproteins, growth factors, and
proteoglycans. Growth factors (such as osteocalcin, osteonectin, and
bone sialoprotein) play important roles in osteoid formation,
mineralization, and bone remodeling. The organic matrix gives bone
its form and provides resistance to tensile forces.
 BONE RE-MODELING

• This is a physiological process in which old or damaged bone is

removed by osteoclasts and then replaced by new bone formed by
osteoblasts.
• There is a tight coupling of bone formation to bone re-sorption to
ensure no net change in bone mass or quality after each remodeling.
• It requires coordinated action of the four types of bone cells.

• The process involves four major distinct but overlapping phases:

 BONE RE-MODELING
Phase 1: INITIATION/ACTIVATION of bone remodeling at a specific
site. As a result of events such as microfracture, mechanical loading, or
low calcium due to pregnancy or a deficient diet, the activation phase
begins.
This prepares the bone for remodelling by forming the BRC and
recruiting osteoclast precursors, which are subsequently activated by
RANKL and M-CSF and attach to the bone surface.

Phase 2: BONE RESORPTION and concurrent recruitment of

osteoprogenitors. Bone resorption represents the predominant event, but
the recruitment of mesenchymal stem cells (MSCs) and/or
osteoprogenitors into the BRC is also initiated.
Resorption then begins, with osteoclasts degrading the bone and
liberating growth factors trapped within the matrix before undergoing
apoptosis. Macrophages clear away the debris from the resorption pit and
a transition to the formation phases begins.
 BONE RE-MODELING
Phase 3: OSTEOID SYNTHESIS -- osteoblast differentiation and
function. Excavated bone is replaced with osteoid (a collagenous matrix)
produced by osteoblasts.

Phase 4: MINERALIZATION OF OSTEOID and completion of bone

remodeling. The osteoid is mineralized, and the bone remodeling cycle is
concluded. This is mineralised over the following 3–6 months by
osteoblasts secreting matrix vesicles that establish an environment
conducive to mineralisation by increasing the concentration of calcium
and phosphorous ions.
During this process, some osteoblasts become trapped and undergo
osteocytogenesis whilst others undergo apoptosis or become bone lining
cells
Postmenopausal Osteoporosis
Caused by a decline in Oestrogen levels associated with
menopause.

This deficiency causes an increase in osteoclast activity by

increasing RANKL and M-CSF expression and inhibiting
osteoclast apoptosis.