BONE
• Specialized connective tissue composed
of bone matrix (calcified ECM)
Bone tissue
• Provides support
• Protect vital organs (cranial and thoracic
cavities)
• Encloses internal (medullary) cavities
containing bone marrow
• Reservoir for calcium, phosphate, and
other ions that can be stored and
release to maintain concentrations in
body fluids
• Three (3) major cell types:
o Osteocytes (Gr. osteon, bone;
kytos, cell)
§ found in the cavities
(lacunae) between bone
matrix layers (lamellae),
with cytoplasmic
processes in small
canaliculi (L. canalis,
canal) that extend to
the matrix
o Osteoblasts (osteon; Gr. blastos,
germ)
§ Growing cells which
synthesize and secrete
organic components of
matrix
o Osteoclasts (osteon; Gr. klastos,
broken)
§ giant, multinucleated
cells involved in
removing calcified bone
matrix and remodeling
bone tissue
• Endosteum
o internal surface surrounding the
marrow cavity
o layers of connective tissue
containing osteogenic cells
• Periosteum
o External surface
o Layers of CT containing
osteogenic cells
Bone cells
Osteoblasts
• Originates from mesenchymal stem cells
• Produce organic components of bone
matrix (type I collagen fibers,
proteoglycans, and matricellular
glycoproteins such as osteonectin)
• are polarized cells with ultrastructural
features denoting active protein
synthesis and secretion during process
of matrix synthesis and calcification
• release membrane-enclosed matrix
vesicles rich in alkaline phosphate and
other enzymes
o matrix vesicles raise local
concentration of PO43- ions
• Active osteoblasts
o Located exclusively at the
surfaces of bone matrix, which
are bound by integrins, and
forming single layer of cuboidal
cells joined by adherent and gap
junctions
• Bone lining cells
o Flattened osteoblasts that cover
the matrix surface
• Majority of osteoblasts undergo
apoptosis when synthetic activity is
completed
• Osteoid
o Layer of unique collagen-rich
material between the osteoblast
layer and preexisting bone
surface
o Produced when matrix
components are secreted in the
cell surface and come in contact
with the bone matrix
o Calcium salts
§ Responsible of bone
appositional growth
• Osteocalcin
o a Vitamin K-dependent
polypeptide, noncollagen
protein secreted by osteoblasts
o binds and concentrates Ca2+
Osteocytes
• differentiated from osteoblasts that
became trapped with the material they
secrete
• significantly less rER; smaller Golgi
complexes; and more condensed nuclear
chromatin than osteoblasts
• some included proteins: paracrine and
endocrine (both help regulate bone
remodeling
• the cells extend many long dendritic
processes during the transition of
osteoblasts to osteoclasts; also become
surrounded by calcifying matrix
• also communicate with nearby
osteoblasts and bone lining cells via gap
junctions at the ends of their processes
• maintain the calcified matrix
• death if followed by rapid matrix
resorption
Osteoclasts
• very large, motile cells, multinucleated
(essential for matrix resorption during
bone growth and remodeling)
• originates from the fusion of bone
marrow-derived monocytes, causing its
characteristics
• osteoclasts development (formation and
activity) requires two polypeptides
produced by osteoblasts
o macrophage-colony-stimulating
factor (M-CSF)
o receptor activator of nuclear
factor-kB ligand (RANKL)
• Resorption lacunae (or Howship lacunae)
o Enzymatically etched
depressions or cavities in the
matrix
o Where osteoclasts on the bone
surface lie during bone
resorption
• Osteoclast activity is controlled by local
signaling factors from other bone cells
Bone Matrix
• About 50% of the dry weight of bone
matrix is inorganic materials;
o Calcium hydroxyapatite; most
abundant
o Bicarbonate, citrate,
magnesium, potassium, sodium
ions
o Significant quantities of
noncrystalline calcium
phosphate
o Surface of hydroxyapatite
crystals are hydrated; facilitating
exchange of ions between
minerals and fluids
• Organic matter embedded in the
calcified ECM is 90% type I collagen; also
includes small proteoglycans and
osteonectin (multiadhesive
glycoproteins)
• Osteocalcin
o calcium binding proteins
• osteocalcin and phosphatases released
from cells in matrix vesicles promote
calcification of the matrix
• association of minerals with collagen
fibers during calcification provides
hardness and resistance required for
bone function
• decalcified bone matrix is usually
acidophilic due to high collagen content;
decalcified bone becomes soft and
pliable like connective tissues but can
still hold its shape
Periosteum and Endosteum
• connective tissue covering the external
and internal surfaces of all bones
Periosteum
• with an outer fiber layer of dense
connective tissue containing mostly
bundled type I collagen and also
fibroblasts and blood vessels
• Perforating (or Sharpey) fibers
o bundles of periosteal collagen
o penetrate the bone matrix;
 o bind the periosteum to the
bone
• periosteum’s inner layer is cellular;
osteoblasts, bone lining cells, and
osteoprogenitor cells (mesenchymal
stem cells)
Endosteum
• very thin internal layer
• covers small trabeculae of bony matrix
that project into the marrow cavities
• also contains osteoprogenitor cells,
osteoblasts, bone lining cells, but within
a sparse, delicate matrix of collagen
fibers
Types of Bone
• Compact (cortical) bone
o dense area near the surface
o 80% of the total bone mass
• Cancellous (trabecular) bone
o 20% of the bone mass
• Microscopic level of compact and
cancellous bone shows two (2) types of
organization:
o Lamellar bone
o Woven bone
In long bones:
Epiphyses (Gr. epiphysis, an excrescence)
o Bulbous ends of long bones
o Composed of cancellous bone covered
by a thin layer of compact cortical bone
Diaphysis (Gr. diaphysis, a growing between)
o Cylindrical part of long bones
o Almost totally dense compact bone with
a thin region of cancellous bone on the
inner surface around the central marrow
cavity
In short bones:
o wrist, ankles
o Have cores of cancellous bone
surrounded completely by compact
bone
In flat bones:
o Flat bones that form calvaria (skullcap)
have two (2) layers of compact bone
(plates) and separated by a thick layer of
cancellous bone (diploë)
Lamellar bone
• Common organization of compact and
cancellous bone in adults
• Characterized of multiple layers of
lamellae (3-7 um thick)
• Lamellae
o Parallel sheets or concentrically
around a central canal
o In each lamella, type I collagen
are aligned
• Osteon (or Haversian system)
o Refers to the complex of
concentric lamellae
o Surrounding a central canal that
contains small blood vessels,
nerves, and endosteum
o All cells of an osteon receive
nutrients and oxygen from
vessels in the central canal
o Cement line
§ Outer boundary of each
osteon that includes
many more noncollagen
proteins in addition to
mineral and collagen
• Lacunae
o Found between successive
lamella; Each one with osteocyte
• Perforating canals (or Volkmann canals)
o have few concentric lamella
o all central osteonic and
perforating canals form when
matrix is laid down around areas
with preexisting blood vessels
• Interstitial lamellae
o Numerous, irregularly shaped
groups of parallel lamellae
scattered among the intact
osteons
 o Lamellae remaining from
osteons partially destroyed by
osteoclasts during growth and
remodeling of bone
• External circumferential lamella
o Immediately beneath the
periosteum
• Inner circumferential lamellae
o Around the marrow cavity
Bone remodeling
• Occurs continuously throughout life
• In compact bone, remodeling resorbs
parts of old osteons and produces new
ones
• 5%-10% of bones in healthy adults turns
over annually
Woven bone
• Nonlamellar and characterized by
random disposition of type I collagen
fibers
• First bone tissue to appear in embryonic
development and in fracture repair
• Usually temporary and replaced by
lamellar bone in adults
• Typically has a lower mineral content
and higher proportion of osteocytes
than mature lamellar bone
o Reflects that immature woven
bone forms more quickly but
has less strength than lamellar
bone
Osteogenesis (or bone development)
Occurs by one of two processes
• Intramembranous ossification
o Osteoblasts differentiate
directly from mesenchyme and
begin secreting osteoid
• Endochondral ossification
o Preexisting matril of hyaline
cartilage is eroded and invaded
by osteoblasts, then begin
osteoid production
• In both processes, woven bone is
produced first and then replaced by
stronger lamellar bone
Intramembranous ossification
• Which most flat bones begin to form
o Takes place within condensed
sheets of embryonic
mesenchymal tissue
• Most bones of the skull, jaws, scapula,
clavicle are formed embryonically by
intramembranous ossification
• Ossification centers
o Where bone formation begins
o Areas in which osteoprogenitor
cells arise, proliferate, and form
incomplete layers of osteoblasts
around a network of developing
capillaries
• Fontanelles (or soft spots) on the head
of newborns are areas of the skull in
which the membranous tissue is not yet
ossified
Endochondral ossification (Gr. endon, within;
chondros, cartilage)
• Takes place within hyaline cartilage
shaped as a small version of the bone to
be formed
• Forms most bones of the body and
studied in long bones
• Bone collar
o Produced by osteoblasts that
differentiate within the
perichondrium (trans. To
periosteum) around the
cartilage model diaphysis
• Primary ossification center
o forms in the diaphysis
o beginning in many embryonic
bones as early as the first
trimester
• Secondary ossification center
o Appear later at the epiphyses of
the cartilage and develop in a
similar manner
• After the primary and secondary
ossification centers, two (2) regions of
cartilage remain:
o Articular cartilage
§ within the joints
between long bones
during adult life
o Epiphyseal cartilage (or
epiphyseal plate/ growth plate)
§ Connects each epiphysis
to the diaphysis and
allows longitudinal bone
growth
§ Responsible for the
growth in length of
bone and disappears
upon development at
adulthood (age 20)
• Starting with the cartilage and farthest
from the ossification center in the
diaphysis:
o Zone of reserve (or resting)
cartilage
§ Composed of typical
hyaline cartilage Bone remodeling and repair
o Proliferative zone
§ Cartilage cells divide
repeatedly
§ Enlarge and secrete
more type II collagen
and proteoglycans
§ Become organized into
columns parallel to the
long axis of bone
o Zone of hypertrophy
§ Contains swollen,
terminally differentiated
chondrocytes which
compress the matrix
into aligned spicules
and stiffen it by
secretion of type X
collagen
o Zone of calcified cartilage
§ Chondrocytes about to
undergo apoptosis
release matrix vesicles
and osteocalcin to begin
matrix calcification by
the formation of
hydroxyapatite crystals
o Zone of ossification
§ Where bone tissue first
appears
§ Osteoblasts settle in a
layer over the spicules
of calcified cartilage
matrix and secrete
osteoid which becomes
woven bone; this woven
bone is remodeled as
lamellar bone
• Appositional growth
o Growth in the circumference of
long bones through the activity
of osteoblasts developing from
osteoprogenitor cells in the
periosteum
o Begins with the formation of the
bone collar on the cartilaginous
diaphysis
• Bone turnover
o Very active in young children
(200x faster than adults)
• Bone remodeling
o Continuous renewal of skeleton
in adults
o Involves coordinated, localized
cellular activities for bone
resorption and bone formation
• Bone repair
o Bone has excellent capacity for
repair because it’s well
vascularized and it contains
osteoprogenitor stem cells in the
periosteum, endosteum, and
marrow
o Signaling molecules and
processes active in bone
remodeling after a fracture or
other damage uses cells
 • Callus
o Soft callus of fibrocartilage-like
tissue produced by the
activation of periosteal
fibroblasts
o Hard callus of woven bone
replaces the soft callus and soon
remodeled into lamellar bone
Metabolic role of bone
• Skeleton serves as calcium reservoir
containing 99% of body’s total calcium
• Concentration of calcium in blood and
tissues is generally stable due to the
continuous interchange between blood
calcium and bone calcium
• Ca2+ mobilization is regulated mainly by
paracrine interactions among bone cells
• Polypeptide hormones influencing
calcium homeostasis:
o Parathyroid hormone (PTH)
§ Raises low blood
calcium levels by
stimulating osteoclasts
and osteoblasts to
resorb bone matric and
release calcium ions
o Calcitonin
§ Produced within the
thyroid gland
§ Reduce elevated blood
calcium levels by
opposing the effects of
PTH in bone
Joints
• Regions where adjacent bones are
capped and held together by other
connective tissues
• Synarthoses (Gr. syn, together; arthrosis,
articulation)
o determines degree of
movement between bones
o allow limited or no movement
o subdivided into fibrous and
cartilaginous joints
o unites skull bones in adults
Major subtypes of synarthroses:
• sutures
o thin layers of dense
connective tissue with
osteogenic cells; unites
skull bones in children
• syndesmoses
o join bones by dense
connective tissue
• symphyses
o have a thick pad of
fibrocartilage between
the thin articular
cartilage covering the
ends of the bones
o all symphyses
(intervertebral discs,
pubic symphysis) occur
in the midline of the
body
Intervertebral discs
• large symphyses between the
articular surfaces of successive
bony vertebral bodies
• annulus fibrosus
o outer portion of each
discs
o consists of concentric
fibrocartilage laminae;
collagen fibers are
arranged orthogonally
(intersecting or lying at
right angles) in adjacent
layers
• nucleus pulposus
o gel-like body situated in
the center of the
annulus fibrosus
o allows each disc to
function as shock
absorber
Joints are classified as diarthroses

Diarthroses
• permit bone movement
• elbows and knees unite long bones and
allow great mobility
• ligaments and dense connective tissue
maintain alignment of bones
• joint cavity
o enclosed by the capsule
o contains synovial fluid (clear,
viscous liquid)
o lined by synovial membrane
• synovial membrane
o (specialized connective tissue)
o extends folds and villi into the
joint cavity
o produces synovial fluid
characterized by two specialized cells:
o macrophage-like synovial cells
(or type A cells)
§ derived from blood
monocytes
§ remove wear-and-tear
debris from the synovial
fluid
§ represents 25% cell
lining of the synovium
§ important in regulating
inflammatory events
within diarthrotic joints
o fibroblastic synovial cell (or type
B cells)
§ produce abundant
hyaluronan and smaller
amounts of
proteoglycans
§ transported by water
from the capillaries into
the joint cavity to form
synovial fluid
• synovial fluid
o lubricates the joint
o reduce friction on all internal
surfaces
o supplies nutrients and oxygen to
articular cartilage