Advances in the Endocrines of

Bone Physiology in Animals

Presented by-
Dilip Kumar Swain,
Ph.D Scholar, DCP,
NDRI, KARNAL.
 Outline of Presentation
• Basic bone structure
• Bone cells
• Osteoblast
• Osteoclast
• Osteoblast- Osteoclast interaction
• Endocrine regulation of bone
• Bone remodelling
• Fracture healing and bone repairing
 Normal Bone Structure

• Lamellar

– Cortical or Compact bone

– Cancellous or spongy bone or Trabecular

bone
• The matrix
– 40% organic
• Type 1 collagen (tensile strength)

• Proteoglycans (compressive strength)

• Osteocalcin / Osteonectin

• Growth factors/ Cytokines/ Osteoid

– 60% inorganic
• Calcium hydroxyapatite
Comparision between Compact & Spongy
Bone
 Bone Cells
• Make up only 2% of bone mass:

– Osteocytes

– Osteoblasts

– Osteoprogenitor Cells

– Osteoclasts
Structure of Long bone
Structure of Bone
Osteon
Dynamic Structure of Haversian
System
Simple Figure to Explain HS
The blue arrows indicate the osteoblasts.
The yellow arrows indicate the bone
matrix they’ve just secreted.
Osteoclast and Bone Resoption
 Parathyroid Hormone
• Released by the cells of the
parathyroid gland in response to
low blood [Ca2+].
Causes blood [Ca2+] to increase.
• PTH will bind to osteoblasts & this will cause :
• The osteoblasts will decrease their activity and they will release
a chemical known as osteoclast-stimulating factor.
• Osteoclast-stimulating factor will increase osteoclast activity.
• PTH increases calcitriol synthesis which increases Ca2+
absorption in the small intestine.
• PTH decreases urinary Ca2+ excretion and increases urinary
phosphate excretion.
 Decreased Blood [Ca2+]

Increased PTH release by

parathyroid gland

Binds to osteoblast
causing decreased Decreased Ca2+
osteoblast activity & Increased calcitriol excretion
release of osteoclast- synthesis
stimulating factor

OSF causes increased Increased intestinal

osteoclast activity Ca2+ absorption

Decreased bone deposition

and increased bone
resorption Increased Blood [Ca2+]
 Calcitonin
• Released by the C cells of the thyroid gland in
response to high blood [Ca2+].
• Calcitonin acts to “tone down” blood calcium levels.
• Calcitonin causes decreased osteoclast activity which
results in decreased break down of bone matrix and
decreased calcium being released into the blood.
• Calcitonin also stimulates osteoblast activity which
means calcium will be taken from the blood and
deposited as bone matrix.

The thyroid
follicles on the
right. The arrow
indicates a C
cell
 Calcitonin Negative Feedback
Loop

Increased Blood [Ca2+] Increased calcitonin release

from thyroid C cells.

Decreased osteoclast activity

Increased osteoblast activity

 Sex Steroids and Bone
• Optimal bone mass and density
• Epiphyseal growth and plate closure
• Post menopausal osteoporosis
• Enhances osteoblastic activity
• Estrogen mediates most of the functions
via cytokines and growth factor
• Progesterone enhances osteoblastic activity
• Role of testosterone remains obscure
 Stimulators of Bone Resorption
• IL-6, IL-8, IL-11
• TNF
• EGF
• PDGF
• FGF
• LIF
• M-CSF
• GM-CSF
• PG
(Matuso Koichi et al.,2008)
 Stimulators of Bone Formation

• IGF

• TGF

• PDGF

• FGF

• Bone morphogenetic proteins

(Gooi et al.,2008)
 Inhibitors of bone resorption

• IFN-

• IL-4

(Natalie A. Sims et al.,2008)

 Factors affecting Bone Turnover
• Oestrogen
– Gut - increased absorption
– Bone - decreased resorption
• Glucocorticoids
– Gut - decrease absorption
– Bone - increased resorption / decreased
formation
• Thyroxine
– Stimulates formation and resorption
– Net resorption
Contd...

• Local stresses

• Electrical stimulation

• Environmental
– temp

– oxygen levels

– acid/base balance
BONE CELLS
Structure of Osteoclast

(Naoyuki Takahasi et al.,2008)

Contd…
• Acid phosphatase tartarate resistant
• Attached to the site of resorption by
integrin via av3 receptors
• Ligands of attachment include
Osteopontin, bone sialoproteinType I
collagen, osteonectin & thrombospondin
• Cytokines IL-1, TNF-, M-CSF – Inhibitors
of osteoclast apoptosis
• Estrogen – potential mediator of
osteoclast apoptosis
Role of Osteoblast in Osteoclast
formation

(Chambers et al., 2006)

Structure of OPG/OCIF

OPG– OSTEOPROTOGERIN
OCIF—OSTEOCLAST INHIBITORY FACTOR

(Chambers et al., 2006)

RANKL-RANK Interaction
during Osteoclastogenesis

(Chambers et al., 2006)

DC-STAMP is involved in
Fusion of Pre-osteoclast

(Yagi et al., 2007)

Molecular Mechanism of Osteoclast
Differentiation & Activation

(Yagi et al., 2007)

Activation of c-jun for
Osteoclastogenesis

(Yagi et al., 2007)

Osteoclastogenesis

(Takayanagi, 2007)
Neural Osteoclastogenesis

(Togari et al.,2008)
 Signaling Pathways of
Osteoclastic Differentiation

(Takayanagi, 2007)
 BONE
REMODELING
 Remodeling
• The adult skeleton:
– maintains itself

– replaces mineral reserves

• Remodeling:
– recycles and renews bone matrix

– involves osteocytes, osteoblasts, and

osteoclasts
 Key Concepts
• Bone continually remodels, recycles, and
replaces.
• Turnover rate varies.
• If deposition is greater than removal,
bones get stronger.
• If removal is faster than replacement,
bones get weaker.
 Contd…..
• Osteocytes sense the mechanical strains
• Remodeling is initiated via through
activation of second messengers.
• Glucose-6-PO4 dehydrogenase, nitric
oxide and IGF-1 are key players.
• Includes both growth and shaping of
bones.
• Initiated at specific units – Basic
multicellular units(BMU)
Bone Remodeling
• Bone is a
dynamic tissue.
• Wolff’s law
holds that bone
will grow or
remodel in
response to the
forces or
demands placed
on it.
General Description of Bone
Remodelling
(Matuso Koichi et al.,2008)
(Koichi et al., 2008)
Bidirectional Signaling by Osteoblast &
Osteoclast which Determines
Osteoblastic Activity
BONE\BMURemodel.swf
 Bone Remodeling Cycle (1)
Endosteal sinus

Monocyte

Pre-osteoclast
Pre-osteoblast

Osteoclast

Osteoblast Bone-lining cell

Osteocyte Macrophage

Osteoid

New bone

Old bone
 Bone Remodeling Cycle (2)
Endosteal sinus

Monocyte

Pre-osteoclast
Pre-osteoblast

Osteoclast

Macrophage Osteoblast Bone-lining cell

Osteocyte

Osteoid

New
bone

Old
bone
Bone Remodeling Cycle (3)
Pre-osteoblasts
Monocytes
Osteoblasts
Osteoclasts
Osteocytes
Why might you suspect
someone whose been a
powerlifter for 15 years to
have heavy, massive
bones, especially at the
point of muscle insertion?

Astronauts tend to
experience bone atrophy
after they’re in space for
an extended period of
time. Why?
Fracture Repair
& Bone
Modelling
Fracture Repair
Step 1:
A. Immediately after the fracture,
extensive bleeding occurs. Over
a period of several hours, a large
blood clot, or fracture hematoma,
develops.
B. Bone cells at the site become
deprived of nutrients and die.
The site becomes swollen,
painful, and inflamed.

Step 2:
A. Granulation tissue is formed as the hematoma is infiltrated by capillaries and
macrophages, which begin to clean up the debris.
B. Some fibroblasts produce collagen fibers that span the break, while others
differentiate into chondroblasts & begin secreting cartilage matrix.
C. Osteoblasts begin forming spongy bone.
D. This entire structure is known as a fibrocartilaginous callus & it splints the broken
bone.
 Fracture
Repair
• Step 3:
A. Bone trabeculae
increase in number &
convert the
fibrocartilaginous callus
into a bony callus of
spongy bone. Typically
takes about 6-8 weeks
for this to occur.

• Step 4:
A. During the next several months, the bony callus is continually
remodeled.
B. Osteoclasts work to remove the temporary supportive structures while
osteoblasts rebuild the compact bone and reconstruct the bone so it
returns to its original shape/structure.
 Conclusion…..
• Bone remodelling is complex.
• Osteoblast & osteocyte communication and
signaling plays the key role in bone
physiology.
• Treatment of bone disorders like
osteoporosis, osteopetrosis, Pagets disease,
osteosarcoma and bone degenerative
disorders.