Chapter 5 BONE CELLS

“Osteogenesis” Osteoblasts

INTRODUCTION • Originate form mesenchymal stem cells

• Produce organic components of the bone matrix
Bone Tissue such as:
• Provide solid support for the body - Type 1 collagen fibers
• protects vital organs such as those in the cranial - Proteoglycans
and thoracic cavities - Matricellular glycoproteins (osteonectin)
• encloses internal (medullary) cavities containing • Deposition of the inorganic components of bone
bone marrow depends
• reservoir of calcium, phosphate, and other ions to
be released/stored to maintain constant
concentrations in body fluids.
Bone

• specialized connective tissue composed of

calcified extracellular material, the bone matrix
• 3 major cell types:
- Osteocytes - found in cavities (lacunae)
between bone matrix layers (lamellae), with
cytoplasmic processes in small canaliculi that
extend into the matrix
- Osteoblasts - growing cells which synthesize
and secrete the organic components of the
matrix
- Osteoclasts - which are giant, multinucleated
cells involved in removing calcified bone
matrix and remodeling bone tissue
Canaliculi - exchanges of metabolites between
osteocytes and blood capillaries depend on
communication through this.
Endosteum – connective tissue containing osteogenic
cells lining the internal surface of the bone
Periosteum – connective tissue lining the external surface
of the bone.
Bone matrix – softened by immersion in a decalcifying
solution before paraffin embedding.
Active osteoblasts
- Located at the surfaces of bone matrix, bound
by integrins, forming cuboidal cells joined by
adherent and gap junctions
• Differentiate as osteocyte entrapped in matrix-
bound lacunae, some cover the matrix surface as
bone lining cells when synthetic activity is
completed, and majority undergo apoptosis.
• During matrix synthesis and calcification:
- Secretes matrix components at the cell
surface in contact with existing bone matrix,
producing a layer of unique collagen-rich
material called osteoid (figure 8-3)
- Deposition of calcium salts into the newly
formed matrix completes this process of bone
appositional growth.
• Process of matrix mineralization
Osteoblasts
secrete secrete

Vitamin K-dependent Matrix vesicles rich in

polypeptide osteocalcin + alkaline phosphatase and
glycoproteins other enzymes that raises
the local concentration of
binds to
phosphate ions.
Calcium ions
High
High concentration
concentration Matrix vesicles serve as
foci for the formation of
Concentrates the mineral hydroxyapatite crystals –
locally fist step in calcifications

Crystals grow rapidly producing a

confluents mass of calcified material
embedding the collagen fibers and
proteoglycans
 Osteoclasts

• very large, motile cells with multiple nuclei that

• Origin from the fusion of bone marrow-deprived
• Osteoclasts
• Resorption lacunae (Howship lacunae) – an
Active osteoclasts
Osteocytes
• Differentiated from osteoblast
• Enclosed singly within the lacunae
• Extends many long dendritic processes –
surrounded by calcifying matrix – occupying the
many canaliculi – where diffusion of metabolites
bet. osteocytes and blood vessels occur
• Communicates with nearby osteoblasts and bone
lining cells via gap junctions at the ends of their
processes – allowing osteocytes to serve as
mechanosensors – detecting the mechanical laod
on bone as well as stress-or-fatigue-induced
microdamage and trigger remedial activity in
osteoblasts and osteoclasts.
• exhibit less RER, smaller Golgi complexes, more
condensed nuclear chromatin than osteoblasts
• express many different proteins that help regulate
bone remodeling.
are essential for matrix resorption during bone
growth and remodeling.
monocytes.
development requires two
polypeptides produced by osteoblasts:
1. Macrophage-colony-stimulating factor (M-
CSF)
2. Receptor activator of nuclear factor-kB
ligand (RANKL)
enzymatically etched depressions or cavities in
the matrix where osteoclasts lie when undergoing
resorption.
▪ The membrane domain that contacts the bone
forms a circular sealing zone that binds the
cell tightly to the bone matrix and surrounds
an area with many surface projections called
the ruffled border.
▪ Pumps protons to acidify and promote
dissolution of the adjacent hydroxyapatite,
and releases matrix metalloproteinases and
other hydrolytic enzymes form lysosome-
related secretory vesicles for the localized
digestion of matrix proteins.
▪ Regulated by local signaling factors form
other bone cells such as osteoblasts activated
by parathyroid hormone to produce MCSF,
RANKL, and others to regulate the formation
activity of osteoclasts.
Bone Matrix • Flat bones (calvaria of the skull)
- Have two layers of compact bone
• 50% of dry weight is inorganic materials
separated by a thicker layer of cancellous
• Abundant is Calcium hydroxyapatite – others bone called diploe.
such as bicarbonate, citrate, magnesium,
• Compact and Cancellous bones two types of
potassium, and sodium ions.
organization:
• Hydroxyapatite crystals are hydrated to facilitate a. Mature lamellar bone – with matrix
the exchange of ions between the mineral and existing as discrete sheets
body fluids. b. Woven bone – newly formed with
• Type 1 collagen – 90% embedded in the calcified randomly arranged components
matrix but also includes small proteoglycans and
mulit-adhesive glycoproteins such as Lamellar bone
osteonectin.
• Characterized by multiple layers or lamellae of
• Calcification of the matrix – promoted by
calcified matrix
osteocalcin and the phosphatases released form
• Organized as parallel sheets or concentrically
cells in matrix vesicles
around a central canal
• Other tissues rich in type 1 collagen lack
• Each lamella have type 1 collagen fibers aligned
osteocalcin and matrix vesicles thus do not
orthogonally, which causes birefringence with
normally become calcified.
polarizing light microscopy and the alternating
• Association of minerals with collagen fibers –
bright and dark layers are due to the changing
provides the harness and resistance required for
orientation of collagen fibers in the lamellae.
bone function
• Decalcified bone matric is acidophilic
Periosteum and Endosteum

• with an outer fibrous layer of dense connective

tissue containing bundled type 1 collagen,
fibroblasts and blood vessels.
• Perforating (Sharpey) fibers – periosteal
collagen that penetrate the bone matrix and bind
the periosteum to the bone.
• Periosteal blood vessels – penetrate the bone
carrying metabolites to and from bone cells.
• Periosteum’s inner layer – includes osteoblasts,
bone lining cells, and mesenchymal stem cells
called osteoprogenitor cells – produce new
osteoblasts for bone growth and repair.
• Endosteum – covers small trabeculae of bony
matrix that project into the marrow cavities.

Types of Bone

• Compact (cortical) bone – represents 80%

of the total bone mass
• Cancellous (trabecular) bone – constitute
20% of total bone mass
• Epiphyses – the bulbous end of long bones
composed of cancellous bone covered by a
thin layer of compact cortical bone
• Diaphysis – cylindrical part almost totally
dense compact bone, with a thin region of
cancellous bone on the inner surface around •
the central Marrow cavity •
• Short bones (wrist and ankle) •
- Have cores of cancellous bone •
surrounded completely by compact
•
bone
•
•
• Osteon (Haversian system) Bone Remodeling (compact bone)
- Complex of concentric lamellae
Osteoclasts remove old bone
surrounding a central canal that and form small, tunnel-like
contains small blood vessels, nerves, cavities
and endosteum.
- Between successive lamellae are tunnels quickly invaded by
lacunae – each with one osteocyte – osteoprogenitor cells from the
endosteum or periosteum and
all interconnected by the canaliculi sprouting loops of capillaries
containing the cell’s dendritic
processes. osteoblasts develop, line the wall of the tunnels, and
- All cells receive nutrients and begin to secrete osteoid in a cyclic manner, or forming
oxygen from vessels in the central a new osteon with concentric lamellae of bone and
trapped osteocytes.
canal.
- Canals also communicate with one
another through transverse
perforating canals (or Volkmann
canals)
- Interstitial lamellae – irregularly
shaped groups of parallel lamellae
scattered among the intact osteons,
which are remains form osteons
partially destroyed by osteoclasts
during growth and remodeling of
bone.
- compact bone also have parallel
lamellae organized as multiple
external circumferential lamellae
immediately beneath the periosteum
and fewer inner circumferential
lamellae around the marrow cavity

Woven Bone

• nonlamellar and characterized by random

disposition of type 1 collagen fibers and is the
first bone tissue to appear in embryonic
development and in fracture repair.
• Temporary and replaced in adults by lamellar
bone except in near the sutures of the calvaria and
in the insertions of some tendons

OSTEOGENESIS

• Occur by one of the two processes

1. Intramembranous ossification –
osteoblasts differentiate directly form
mesenchyme and begin secreting osteoid.
2. Endochondral ossification – a preexisting
matrix of hyaline cartilage is eroded and
invaded by osteoblasts, which then begin
osteoid production.
 Endochondral Ossification
Intramembranous ossification
• most flat bones begin to form, takes place within
condensed sheets (“membranes”) of embryonic
mesenchymal tissue
• bones of the skull and jaws, scapula and clavicle
bone formation begins in ossification centers, areas
in which osteoprogenitor cells arise, proliferate, and
form incomplete layers of osteoblasts around a
network of developing capillaries
Osteoid secreted by the osteoblasts calcifies, forming
small irregular areas of woven bone with osteocytes
in lacunae and canaliculi
Continued matrix secretion and calcification enlarges
these areas and leads to the fusion of neighboring
ossification centers
anatomical bone forms gradually as woven bone
matrix is replaced by compact bone that encloses a
region of cancellous bone with marrow and larger
blood vessels
Mesenchymal regions that do not undergo
ossification give rise to the endosteum and the
periosteum of the new bone
• cranial flat bones, lamellar bone formation
predominates over bone resorption at both the
internal and external surfaces
• Internal and external plates of compact bone
arise, while the central portion (diploë) maintains
its cancellous nature.
• fontanelles or “soft spots” on the heads of
newborn infants are areas of the skull in which the
membranous tissue is not yet ossified.
• takes place within hyaline cartilage shaped as a
small version, or model, of the bone to be formed
• forms most bones of the body and is especially
well studied in developing long bones, where it
consists of the sequence of events
• this process in the diaphysis forms the primary
ossification center
• Secondary ossification centers appear later at the
epiphyses of the cartilage model and develop in a
similar manner.
• During their expansion and remodeling both the
primary and secondary ossification centers
produce cavities that are gradually filled with
bone marrow and trabeculae of cancellous bone.
• With the primary and secondary ossification
centers, two regions of cartilage remain:
1. Articular cartilage - within the joints between
long bones which normally persists through
adult life
2. specially organized epiphyseal cartilage
(also called the epiphyseal plate or growth
plate), which connects each epiphysis to the
diaphysis and allows longitudinal bone
growth
• Epiphyseal cartilage
- responsible for the growth in length
of the bone and disappears upon
completion of bone development at
adulthood
- it is possible to determine the “bone
age” of a young person, by noting
which epiphyses have completed
closure.
• Epiphyseal growth plate distinct regions:
1. zone of reserve (or resting) cartilage is
composed of typical hyaline cartilage
2. In the proliferative zone, the cartilage cells
divide repeatedly, enlarge and secrete more
type II collagen and proteoglycans, and
become organized into columns parallel to
the long axis of the bone.
3. zone of hypertrophy contains swollen,
terminally differentiated chondrocytes which
compress the matrix into aligned spicules and
stiffen it by secretion of type X collagen.
Unique to the hypertrophic chondrocytes in
developing (or fractured) bone, type X
collagen limits diffusion in the matrix and
 with growth factors promotes vascularization
from the adjacent primary ossification center
4. zone of calcified cartilage, chondrocytes
about to undergo apoptosis release matrix
vesicles and osteocalcin to begin matrix
calcification by the formation of
hydroxyapatite crystals.
5. zone of ossification bone tissue first appears.
Capillaries and osteoprogenitor cells invade
the now vacant chondrocytes lacunae, many
of which merge to form the initial marrow
cavity. Osteoblasts settle in a layer over the
spicules of calcified cartilage matrix and
secrete osteoid which becomes woven bone
This woven bone is then remodeled as
lamellar bone.
- active in bone remodeling.
• Appositional growth
- Growth in the circumference of long
bones does not involve endochondral
ossification but occurs through the
activity of osteoblasts developing
from osteoprogenitor cells in the
periosteum by this process which
begins with formation of the bone
collar on the cartilaginous diaphysis.
Bone Remodeling and Repair
• The sum of osteoblast and osteoclast activities in
a growing bone constitutes osteogenesis or the
process of bone modeling, which maintains each
bone’s general shape while increasing its mass
• constant remodeling of bone ensures that, despite
its hardness, this tissue remains plastic and
capable of adapting its internal structure in the
face of changing stresses.
• Because it contains osteoprogenitor stem cells in
the periosteum, endosteum, and marrow and is
very well vascularized, bone normally has an
excellent capacity for repair.
• Bone repair after a fracture or other damage uses
cells, signaling molecules, and processes already
• major phases that occur typically during bone
fracture repair include initial formation of
fibrocartilage and its replacement with a
temporary callus of woven bone
Metabolic role of bone
• the skeleton serves as the calcium reservoir,
containing 99% of the body’s total calcium in
hydroxyapatite crystals
• concentration of calcium in the blood (9-10
mg/dL) and tissues is generally quite stable
because of a continuous interchange between
blood calcium and bone calcium
• principal mechanism for raising blood calcium
levels is the mobilization of ions from
hydroxyapatite to interstitial fluid, primarily in
cancellous bone
• two polypeptide hormone target bonce cells to
influence calcium homeostasis
a. Parathyroid hormone (PTH) from the
parathyroid glands raises low blood calcium
levels by stimulating osteoclasts and
osteocytes to resorb bone matrix and release
Ca2+. the PTH effect on osteoclasts is
indirect; PTH receptors occur on osteoblasts,
which respond by secreting RANKL and
other paracrine factors that stimulate
osteoclast formation and activity.
b. Calcitonin, produced within the thyroid
gland, can reduce elevated blood calcium
levels by opposing the effects of PTH in
bone. this hormone directly targets
osteoclasts to slow matrix resorption and
bone turnover.
Joints
• regions where adjacent bones are capped and held
together firmly by other connective tissues
• Joints classified as synarthroses (Gr. syn, together
+ arthrosis, articulation) allow very limited or no
movement and are subdivided into fibrous and
cartilaginous joints, depending on the type of
tissue joining the bones.
• Major subtypes:
a. Synostoses involve bones linked to other
bones and allow essentially no movement. In
older adults synostoses unite the skull bones,
which in children and young adults are held
together by sutures, or thin layers of dense
connective tissue with osteogenic cells.
b. Syndesmoses join bones by dense connective
tissue only. Examples include the
interosseous ligament of the inferior
tibiofibular joint and the posterior region of
the sacroiliac joints.
c. Symphyses have a thick pad of fibrocartilage
between the thin articular cartilage covering
the ends of the bones. All symphyses, such as
the intervertebral discs and pubic symphysis,
occur in the midline of the body.
• Intervertebral discs are large symphyses
between the articular surfaces of successive bony
vertebral bodies.
• Each disc has an outer portion, the annulus
fibrosus, consisting of concentric fibrocartilage
laminae in which collagen bundles are arranged
orthogonally in adjacent layers.
• Situated in the center of the annulus fibrosus, a
gel-like body called the nucleus pulposus allows
each disc to function as a shock absorber
• diarthroses permit free bone movement.
Diarthroses such as the elbow and knee generally
unite long bones and allow great mobility.
• The capsule encloses a sealed joint cavity
containing a clear, viscous liquid called synovial
fluid.
• the joint cavity is lined, not by epithelium, but by
a specialized connective tissue called the
synovial membrane that extends folds and villi
into the joint cavity and produces the lubricant
synovial fluid.
• In different diarthrotic joints the synovial
membrane may have prominent regions with
dense connective tissue or fat.
• Besides having cells typical of connective tissue
proper and a changing population of leukocytes,
this area of a synovial membrane is characterized
by two specialized cells with distinctly different
functions and origins:
1. Macrophage-like synovial cells, also called
type A cells, are derived from blood
monocytes and remove wear-and-tear debris
from the synovial fluid. These modified
macrophages, which represent approximately
25% of the cells lining the synovium, are
important in regulating inflammatory events
within diarthrotic joints.
2. Fibroblastic synovial cells, or type B cells,
produce abundant hyaluronan and smaller
amounts of proteoglycans. Much of this
material is transported by water from the
capillaries into the joint cavity to form the
synovial fluid, which lubricates the joint,
reducing friction on all internal surfaces, and
supplies nutrients and oxygen to the articular
cartilage.