Basic Science of

Bone Cells

Osteoblasts
Osteoblasts are never found individually; they
form clusters of cells on the bone surface
Osteoblasts are active cells with an eccentric
nucleus that is on the opposite side of the bone
surface
A prominent and well-developed endoplasmic
reticulum and Golgi apparatus are present in the
cell
After the osteoblast finishes secreting the
extracellular matrix, the osteoblast becomes
either a resting lining cell or an osteocyte

 Osteoblasts are formed from pluripotential

mesenchymal stem cells.
Osteoblasts are bone lining cells.
Osteoblasts produce matrix proteins (osteoid).
Osteoblasts produce alkaline phosphatase
(marker for bone formation).
Osteoblasts have receptors for a number of
hormones including:
Estrogen (nucleus)
Vitamin D3 (nucleus)
Parathyroid hormone (PTH) (cell surface)

Osteocytes
Osteocytes are formed from osteoblasts
that have become imbedded in the bone
matrix.
Osteocytes have fine cytoplasmic
connections with one another.
Osteocytes have receptors for PTH.
Osteocytes respond to mechanical signals
and send signals for bone remodeling

Osteoclasts
Osteoclasts resorb bone and reside in the
Howship lacunae (usually 1 to 5 osteoclasts are
found
There is a ruffled border where the osteoclast is
in contact with the bone surface (sealing zone)
The area in contact with the bone is called the
subosteoclastic bone-resorbing compartment
Osteoclasts contain abundant Golgi
apparatuses, mitochondria, and lysosomal
enzymes

 The osteoclast acidifies the bone-resorbing

compartment by pumping protons across the
ruffled border via enzyme carbonic anhydrase
As a result of pumping of the protons, there is an
acidic environment, lysosomal enzymes, and
bone matrix to be resorbed
The acidic environment dissolves the
hydroxyapatite crystals, and the lysosomal
enzymes degrade the matrix. Collagen is
degraded by collagenase or cathepsins
As the hydroxyapatite dissolves and the collagen
is broken down, one can measure the collagen
byproducts (hydroxyproline, pyridoxiline, and Ntelopeptide).

 Osteoclasts are giant multinucleated cells.

Osteoclasts are formed from hematopoietic
monocyte stem cell precursor.
Osteoclasts resorb bone to form Howship
lacunae or resorption pits.
Osteoclasts are responsive to osteoblasts
through receptor activator of nuclear factor -kB
ligand (RANKL).
Osteoclasts have receptors for calcitonin
(calcitonin causes osteoclasts to shrink)

Osteocytic osteolysis
Osteocytes have receptors for PTH. When PTH
levels increase, the osteocytes are signaled to
mobilize calcium. The osteocytes mobilize poorly
crystallized calcium salts without damaging the
organic matrix of the bone. Osteocytes pump the
calcium into the extracellular fluid. Simply stated,
the osteocytes mobilize calcium quickly in
response to signaling by PTH without degrading
the bone structure

Osteoclast activation regulation

Osteoclast activation is a complex
process. Osteoclasts have a
hematopoietic monocyte stem cell lineage.
Osteoblasts signal osteoclasts to form and
resorb bone. The osteoblast produces a
molecule called RANKL that sits on the
cell surface of the osteoblast. On the
surface of the osteoclast precursor cell,
there is a receptor called receptor
activator of nuclear factor -kB (RANK).

 RANKL binds to RANK, and in the presence of

macrophage-colony stimulating factor (M-CSF),
there is transformation of the osteoclast
precursors into active osteoclasts. Interleukin-6
(IL-6), which is produced by osteoblasts, signals
osteoclasts to resorb bone. Osteoprotegerin
(OPG) acts as a soluble decoy inhibitor, binds to
RANKL, and does not allow RANKL to bind to
RANK on the surface of the osteoclast precursor
cell. The osteoclast precursor cell does not
become an active osteoclast.

Factors that increase osteoclast

activation include
RANKL
M-CSF

A factor that decrease osteoclast

activation includes
OPG

Osteoblast activation and function

Osteoblasts secrete bone matrix, but they
also play an important role in regulation. In
response to low calcium levels, the C cells
of the parathyroid gland secrete PTH that
binds to the osteoblast and directs the
osteoblast to produce bone. In addition,
the osteoblasts produce RANKL and IL-6.
The RANKL binds to the RANK receptor
on the osteoclast precursor cells, and the
precursor cells form active osteoclasts. IL6 directs the osteoclasts to resorb bone.

 The osteoblasts line the bone surface and

protect the bone from the osteoclasts.
Once stimulated by PTH, the osteoblasts
contract and withdraw from the bone
surface to allow the osteoclasts to attach
to the bone. The osteoblasts secrete
neutral proteases that degrade the surface
osteoid. The osteoclasts then attach to the
bone and resorb the bone matrix and
mineral

Vitamin D
Fat-soluble steroid hormone
Sources
Diet (fatty fish, fortified cereals, bread, and milk)
Skin production; ultraviolet light converts 7dehydrocholesterol to vitamin D3
Liver hydroxylation to 25 hydroxyvitamin D3
Kidney hydroxylation to 1,25 dihydroxyvitamin
D3 (rate limiting step in vitamin D3 production)
Active form is 1,25 dihydroxyvitamin D3
Recommended daily intake is 400 IU to 800 IU

Functions
1. Increases resorption of phosphate in the kidney
proximal tubule
2. Maintains normal extracellular concentrations of calcium
and phosphorus
3. Regulates production of calcium binding protein needed
for calcium absorption
4. Enhances mobilization of calcium stores in bone
5. 1,25 dihydroxyvitamin D3 induces monoctye stem cells
to form osteoclasts
6. 1,25 dihydroxyvitamin D3 tells osteoblasts to produce
RANKL thereby mobilizing osteoclasts

 24,25 dihydroxyvitamin D3 influences

growth plate chondrocyte maturation and
potent mitogen in the growth plate
proliferative zone

Parathyroid hormone (PTH)

Low calcium levels stimulate PTH release from
parathyroid glands through cAMP pathway.
Increased calcium levels inhibit PTH secretion.
PTH binds to osteoblast receptors to increase bone
formation.
PTH signals osteoblasts to produce IL-6 that directs
osteoclast to resorb bone.
PTH decreases phosphorus resorption in the proximal
tubule.
PTH increases distal tubule reabsorption of calcium.
PTH stimulates 1 alpha hydroxylase activity (increase
1,25 dihydroxyvitamin D3).

Calcitonin
Calcitonin is a hormone secreted by parafollicular
cells of the thyroid gland.
Calcitonin function is not understood in humans.
Functions
Causes rapid dissolution of osteoclastic ruffled
border
Inhibits osteoclastic bone resorption
Causes shrinkage of osteoclasts
Calcitonin secretion increases as calcium levels rise.
Calcitonin causes decreased reabsorption of calcium
and phosphorus in the kidney