Lect 04 - Connective Tissue - Bone
Four Tissue Types
Structure & Function
Lect # 4
1. Epithelial tissue
Skeletal Connective Tissue
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Prof Kumlesh K. Dev
Department of Physiology
Lining/barrier of secretory
Skin and mucous membranes
2. Muscle (excitable) tissue
–
–
–
Skeletal (striated) muscle
Smooth muscle
Cardiac muscle
3. Nervous (excitable) tissue
SKELETAL
CARTILAGE
GENERAL
BONE
CELLS
BLOOD
FIBRES
–
–
FLUID
LYMPH
4. Connective tissue (cells, fibres, matrix)
–
–
–
–
GROUND SUBSTANCE
3 Types of Specialised Connective Tissue
─ Specialised Connective Tissue is characterised by
dominance of matrix
3 Types of specialised connective tissue
Brain
Spinal cord
Loose connective tissue
Dense fibrous tissue (Capsule, Ligament, Tendon)
Cartilage & Bone
Blood (originate from bone marrow)
Specialised Connective Tissue
Lect 4
SKELETAL
CARTILAGE
Lect 3
GENERAL
BONE
Lect 5
FLUID
BLOOD
LYMPH
─ 1. Cartilage: semisolid matrix (semi-rigid support)
─ 2. Bone: calcified matrix
─ 3. Blood: liquid matrix
CELLS
Mesenchymal cells
Fibroblasts
Adipocytes (fat cells)
Immune cells
- Macrophages
- Mast cells
- Plasma cells
- Lymphocyte
- Monocyte
FIBRES
GROUND SUBSTANCE
Collagen
Elastin
1
Lect 04 - Connective Tissue - Bone
(1) Cartilage: characteristics
(2) Cartilage: function
─ a semi-rigid dense connective tissue
─ support and flexibility
─ consists of
─ covers bone to give smooth surfaces for movement
─ cells (chondrocytes)
─ reduces friction in joints
─ fibers (dense network of collagen and/or elastin fibers)
─ absorbs shock
─ matrix (proteoglycans, ground substance)
─ involved in development & growth of bones
─ no innervation
─ no lymphatic vessels
─ no blood vessels (avascular)
─ nourished by diffusion of gases and nutrients
Cartilage cells: 3 types
Type
(3) Cartilage: formation (5 steps)
Function
differentiate
1. Mesenchymal cells
─ differentiate into chondroblasts
2. Chondroblasts
─ synthesise ground substance & matrix
1. mesenchymal cells differentiate
ff
chondroblast
divide & grow
2. chondroblasts proliferate & synthesise ground
substance & fibrous extracellular matrix
3. chondroblasts separate into spaces (lacunae)
further divisions
3. Chondrocytes
─ 5 steps of cartilage formation: chondrification
(-genesis)
4. more divisions form clusters (isogenous grps)
y
are embedded in
5. these chondrocytes
extracellular matrix
─ mature cells, embedded in matrix
Remember: ‘B’
before ‘C’ –
chondroBLASTS
before
chondroCYTES
─ in embryogenesis, skeletal system derived
from mesoderm germ layer, most skeleton is
cartilage
─ cartilage replaced by bone (ossification)
2
Lect 04 - Connective Tissue - Bone
• surrounded by its own
secreted matrix
– contain lipid droplets (L)
– rich in glycogen granules
• they synthesise
Cartilage
Matrix
Rough
Endoplasmic
Reticulum
Chondrocyte
– ground substance
Golgi apparatus
– fibrous elements
Secreted
matrix material
─ covers surface of most
cartilage
─ unlike other connective tissues,
cartilage has no blood
vessels or nerves
nerves, except in
perichondrium
Appositional Growth (thickness)
─ continues through adolescence
─ increases cartilage thickness
─ chondroblasts in perichondrium
form chondrocytes which lay
down new matrix to outside
─ cartilage grows in width
Perichondrial
fibroblast
ChondroBlast
─ since cartilage has no blood
supply, it heals slowly
following an injury
(6) Cartilage: growth (2 types)
Interstitial Growth (mass)
─ during childhood & adolescence
─ increases cartilage mass
─ chondrocytes within tissue divide
and deposit more extracellular
matrix
─ mass increased from within
Peric
chondrium
─ perichondrium is a membrane
of dense irregular connective
ti
tissue
• chondrocyte occupies hallow
space
p
((lacuna))
• chondrocyte cytoplasm
(5) Cartilage: the perichondrium ‘surface’
Carttilage
(4) Cartilage: chondrocytes
ChondroCyte
matrix
(7) Cartilage: 4 types
Type
Function
The amounts of collagen & elastic fibres vary in types of cartilage.
1. Hyaline Cartilage
─ most common, weakest of all types
─ flexibility (trachea) & smoothness (articular surfaces)
2. Elastic Cartilage
─ rich in elastic fibers
─ gives support & elasticity (ear)
3 Fibrocartilage
3.
─ dense network of collagen
collagen, strongest of all types
─ movement in all directions (intervertebral disc, knee)
4. Articular Cartilage
─ usually made of hyaline (sometimes fibrocartilage)
─ covers bone ends of movable joints
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Lect 04 - Connective Tissue - Bone
1. Hyaline Cartilage
─
for bone development
─
in embryo, cartilage laid
d
down
th
then replaced
l
db
by b
bone
Adjacent
supporting tissue
(A) Adipocytes
(C) Capillaries
(N) Nerves
─
has perichondrium
Perichondrium (P)
─
condrocytes arranged in
clusters
─
collagen fibers scattered
th
throughout
h t matrix
ti
─
found in joint surfaces, nasal
septum, larynx, trachea,
bronchi, connects ribs to
sternum
2. Elastic Cartilage
─ for support and elasticity
glycogen
y g & lipids
p
but more
─ less g
dense elastic fibers
Perichondrium
─ perichondrium is mainly collagen
─ condrocytes are closely packed &
found singly, rather than clusters
Condrocytes are
arranged in
clusters of 22-4
differentiated cells
clusters
─ for withstanding all
movements
─ no perichondrium
─ chondrocytes arranged in rows
between collagen layers
─ found mainly between the
vertebrae of the spinal column,
intervetebral discs, joint
capsules, ligaments and
tendons
Elastic fibers
─ found in ear pinna, several tubes
e.g. auditory canal, epiglottis,
larynx to keep tubes open
Chondrocytes
4. Articular Cartilage
3. Fibrocartilage
─ has collagen & ground
substance and numerous
strands of fibers
─ elastic bundles ((elastin)) scattered
in matrix
─ covers bone ends of
movable joints
hondrocytes
─ usually made of hyaline
cartilage (sometimes
fibrocartilage)
─ Articular Cartilage
─ no perichondrium
─ no innervation (would be
painful movement)
─ bathed & nourished by
synovial fluid
4
Lect 04 - Connective Tissue - Bone
Disease (I)
Disease (II)
─ cartilage easily damaged with limited repair capabilities
─ OsteroArthritis: degeneration of cartilage joints (articular cartilage)
─ chondrocytes bound in hallow spaces cannot migrate to
damaged areas to make new matrix
─ Dwarfism (Achondroplasia): reduced proliferation of chondrocytes in
long
g bones during
g infancy
y & childhood,, resulting
g in dwarfism.
─ Elastic & Fibrocartilage show less damage or aging
─ Herniated disk: Compression ruptures disk cartilage ring, pushing
into spine
─ Hyaline cartilage easily damaged & has limited repair
ability in perichondrium
─ Tumors: cartilage cells give rise to benign (chondroma) tumors.
Malignant tumors occur in bone, not usually cartilage
─ Articular Cartilage do not repair
─ Scurvy: Vitamin C required to process collagen; Scurvy (Vit C
deficiency) results in defective cartilage and bone
g cartilage
g replaced
p
by
y fibrocartilage
g scar tissue
─ damaged
─ cartilage transplantation, no issues of rejection because:
─ antigenic power of cartilage is low
─ immune system cells poorly diffuse cartilage - matrix acts
as a barrier, prevent entry of lymphocytes &
immunoglobulins
Specialised Connective Tissue
Lect 4
SKELETAL
Lect 3
GENERAL
Lect 5
FLUID
Others
─ Polychondritis: inflammation & degeneration of cartilage
─ Chondromalacia: degeneration joint cartilage (knees)
─ Chondrodysplasia: hereditary bone dysplasia.
─ Costochondritis: inflammation of rib cartilage causing chest pain
─ Tietze’s Syndrome: inflammation of cartilage that joins ribs to
breast bone
Six bone functions
─ Number - 206 bones in adult & about 300 in infants
pp , Movement and Protection
─ 1. Support,
CARTILAGE
BONE
CELLS
Mesenchymal cells
Fibroblasts
Adipocytes (fat cells)
Immune cells
- Macrophages
- Mast cells
- Plasma cells
- Lymphocyte
- Monocyte
BLOOD
FIBRES
Collagen
Elastin
LYMPH
GROUND SUBSTANCE
─ 2. Hematopoiesis - makes Red Blood Cells in red bone
marrow, situated in spongy tissue (medullary cavity)
─ 3. Mineral storage - acts as calcium reservoir, maintains
calcium & phosphorus equilibrium
─ 4. Acid-base balance - buffers blood against excessive pH
changes by absorbing or releasing alkaline salts
─ 5. Detoxification - stores heavy metals and foreign
elements
─ 6. Sound transduction - in mechanical aspect of hearing
5
Lect 04 - Connective Tissue - Bone
Four bones types
─ 1. Long bones: long shaft & two
articular joints; compact bone with
marrow
─ 2. Short bones: cube-shaped,
have thin layer of compact bone
─ Sesamoid bones: special type of
short bone; forms within tendon
(patella)
─ 3. Flat bones: thin & curved, have
two layers of compact bones &
spongy bone (skull, sternum)
─ 4. Irregular bones: thin layers of
compact bone surround spongy
interior (spine, hips)
Four steps of bone formation
• bones are solid network of
– living cells
– collagenous extracellular matrix (type I collagen)
Formation of bone (4 steps) (see Osteoblasts)
─ 1. osteoblasts synthesise & secrete collagen & organic
matrix (osteoid)
─ 2. osteoid then becomes calcified (i.e. calcium deposition)
─ 3.
3 osteoblasts secrete vesicles of alkaline phosphatase (AP)
─ 4. AP causes matrix mineralisation (gives rigidity & strength)
• in rickets & chronic renal failure inadequate calcium and
phosphate ions in osteiod tissue and mineralisation is slow
Bone matrix composition
Bone cells: 4 types
Type
Function
─ bone matrix is composed of:
─ 20% Organic Materials (i.e.
(i e Osteoid from osteoblasts)
─ Type I Collagen fibers (90% of organic osteoid part)
─ Glycosaaminoglycans
─ Ground substance proteoglycans (chondroitin sulphate
& hyaluronic acid)
─ 70% Inorganic Materials Salts
─ Mainly Calcium & Phosphate (in form of hydroxyapatite
crystals)
1. Osteoprogenitor cells
─ bone stem cells
─ generate osteoblasts and osteocytes
2. Osteoblasts
─ bone forming cells
─ immature bone cells
3. Osteocytes
─ inactive osteoblasts
─ most abundant cell found in bone
4. Osteoclasts
─ phagocytic cells
─ erode bone
─ 10% Water
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Lect 04 - Connective Tissue - Bone
Four bone cells types: Osteoprogenitors
Four bone cells types: Osteoblasts
2. Osteoblasts (bone forming cells)
─ immature bone cells
─ contain lots of rough ER for collagen
synthesis
th i
─ make hormones (prostaglandin)
─ decrease numbers in age
1. Osteoprogenitor cells
─ bone stem cells
─ generate
t osteoblasts
t bl t and
d
osteocytes
─ located in periosteum and bone
marrow
Formation of bone (4 steps)
─ 1. osteoblasts synthesise & secrete
collagen (type 1) & organic matrix
(osteoid)
─ 2. osteoid then becomes calcified (i.e.
calcium deposition)
─ 3. osteoblasts secrete vesicles of alkaline
phosphatase (AP)
─ 4. AP causes matrix mineralisation (gives
rigidity and strength)
─ induced to differentiate by growth
facors
─ e.g. particular bone morphogenetic
proteins (BMP)
Osteoprogenitor
Four bone cells types: Osteocytes
3. Osteocytes
─ inactive osteoblasts
O: osteoblasts
Four bone cells types: Osteoclasts
4. Osteoclasts (phagocytic cells)
C: loose collagenous tissue
─
formed in bone marrow from
heamatopoietic
p
stem cells
─
large multi-nucleated phagocytic cells
─
phagocytose collagen & dead
osetocytes
─
secrete organic acids and lysosomal
proteolytic enzymes to erode bone
─
reside resorption bays (Howship's
(Howship s
lacunae)
─ most abundant cell found in bone
─ less ER & smaller than
osteoblasts
─ numerous spider shape
cytoplasmic
─ processes connected by gap
junctions
─ provide bone nutrition
osteocytes
Learn the types
yp of
Fixed Macrophages
1. Dust/Alveolar type (lungs)
2. Histiocytes (connective tissue)
3. Kupffer cells (liver)
4. Microglial cells (nervous)
5. Osteoclasts (bone)
6. Sinusoidal lining cells (spleen)
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Lect 04 - Connective Tissue - Bone
Two bones forms: Woven & Lamellar
Bone exists in 2 main forms
1. Woven bone (immature)
─ osteoblasts
t bl t produce
d
osteoid
t id rapidly
idl
─ forms random collagen fibers in osteoid
─ e.g. fetal bone development, healing
fracture & Paget’s disease
2. Lamellar bone (adult)
─ replaces woven bone (stronger)
─ regular parallel collagen sheets
─ 2 types
─ Compact (cortical) bone
─ Cancellous (medullary) bone
Random pattern
The long bone
─
ends of bones
- Epiphysis
─
shaft of bones
- Diaphysis
─
junction of shaft - Metaphysis
x.
Articular cartilage (see cartilage slides)
─
Periosteum
─
Compact bone
─
Cancellous bone
─
Medullary cavity
Regular pattern
Long bone: 4 main structures
Type
Metaphysis
(junction of shaft)
Function
The long bone: Periosteum
1. Periosteum
─ tough fibrous connective tissue
─ contains osteoprogenitor cells
1. Periosteum
2. Compact bone
─ contains osteoprogenitor cells
─ tough fibrous connective tissue
─ contain trapped osteocytes
─ dense hard outer layer of shaft
3. Cancellous bone
─ fine network of bone
─ ends of long bones (epiphysis)
4. Medullary cavity
─ red marrow (makes red blood cells)
─ yellow marrow (fat/energy storage)
─ plays role in repair
─ cells differentiate into osteoblasts
─ supplied with blood vessels & nerves
─ muscle fibers may adjoin periosteum
─ its collagen fibers merge with those of
tendons & ligaments
Compact bone
Periosteum
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Lect 04 - Connective Tissue - Bone
The long bone: Compact bone
2. Compact (cortical/cortex) bone
– accounts for 80% of bone in skeleton
– forms dense hard outer layer
y of shaft
– made bony column layers (lamellae)
– osteocytes are trapped between
lamellae in spaces (lacunae)
– nutrition provided by system of canals
The long bone: Cancellous bone
3. Cancellous (spongy) bone
– occurs at ends of long bones
(epiphysis)
– consists of fine network of bone,
trabeculae, separated by
interconnecting spaces
– this bone type does not usually contain
Haversian systems
1. lamellae surround Havers canal
which contain blood vessels, lymphatics
& nerves (Haversian
(H
i
systems
t
2. volkmann’s canals run at right angles
to connect Haversian canals
3. between lacunae are fine canals
(canaliculi) which osteocyte processes
can pass through
The long bone: Medullary cavity
4. Medullary cavity
– has thin interconnecting bone (trabeculae)
– number/thickness of trabeculae depends
p
on bone stress exposure (e.g. many
trabeculae in weight-bearing vertebrae)
– spaces between trabeculae occupied bone
marrow
– during age red marrow is mostly replaced
by yellow marrow
– red marrow
makes red blood cells
– yellow marrow
site for fat/adipose (energy) storage
Modelling of Bone (ossification)
Modelling (early in life)
─ changes bone size, shape or both
─ independent action of osteoblasts & osteoclasts
─ bone development controlled by hormones
─ in fetus collagenous tissue replaced by bone
Bone Formation (2 ways):
1. Intramembranous Ossification
– mesenchymal cells create new bone
2. Endochondral Ossification
– replacement of cartilage with bone
– occurs at growth plate (epiphyseal disc)
– osteoblasts use calcified cartilage as
framework to deposit new bone
– 18-25 yrs all cartilage is replaced by bone
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Lect 04 - Connective Tissue - Bone
Endochondral Ossification
– transition between cartilage and new
bone occurs in 6 zones (top-bottom):
– 1. reverse cartilage zone: consists
off hyaline
h li cartilage
til
with
ith
chondrocytes
– 2. proliferation zone: chondrocytes
undergo mitotic divisions
Remodelling of Bone
Reserve
(cartilage)
Proliferation
Maturation
– 3. maturation zone: chondrocytes
increase in size
– 4. hypertrophy/calcification zone:
chondrocytes enlarged & matrix
calcified
Degenerate
– 5. cartilage degeneration zone:
chondrocytes degenerate
Osteogenic
(bone)
Hypertrophy
Remodelling (throughout life)
– not affect size or shape
– involves coupled ostoclast reabsorption followed by
osteoblast deposition
– older/damaged bone replaced by healthy bone
– 5% of bone remodelling at any time
– induced by diet, exercise, lifestyle
– bone under stress tends to be thicker/stronger
– newer bone more resistant to fracture
– balance necessary or bones become too thick/thin
– 6. osteogenic zone: osteoblasts
commence bone formation
Bone Fractures
Bone and Calcium Regulation
─ 99% of body’s Ca2+ in bone (~1 kg)
At fractures:
T Ca2+
Two
C 2 compartments
t
t
1. blood clot forms at fracture site (6-8h)
2. replaced by collagen tissue
1. Bone fluid:
3. chondroblasts lay down cartilage
─
(provisional callus) (2-3 weeks)
2. Mineralised bone:
4. osteoblasts lay down woven bone
(bony callus) (3-4 months)
5. bony callus then remodelled to mature
lamellar bone
fast exchange by pumps
Types of Fractures
- Simple
- Compound
- Comminuted
- Greenstick
- Impacted
- Stress
─
slow exchange by bone resorption
─
osteoclasts phagocytic activity increased & Ca2+
release during low Ca2+ levels
10
Lect 04 - Connective Tissue - Bone
8 Hormones Regulate Bone Growth & Loss
Bone Growth
- activate
ti t osteoblast
t bl t & inhibit
i hibit osteoclast
t
l t function
f
ti
1. Vitamin D
2. Growth Hormone
3. Oestrogen
4. Calcitonin
promote osteoblast differentiation
promote osteoblast function
inhibit osteoclast
inhibit osteoclast
Osteoporosis
– low oestrogen
– loss of osteoclast inhibition
– bone resorption faster than bone deposition
– low bone mass and density
– vertebral and hip fractures common
Bone Loss
- inhibit
i hibit osteoblast
t bl t & activate
ti t osteoclast
t
l t ffunction
ti
5. Cortisol
6. Parathyroid hormone (PTH)
7. Thyroid
8. Vitamin A
promote osteoblast death (apoptosis)
activate osteoclast
activate osteoclast
activate osteoclast
Cartilage & Bone : don’t mix them up !
Learning Outcomes – (Lessons 7 & 8)
Cartilage
Bone
To be able to:
Cells
Cells
1. Mesenchymal cells
2. Chondroblasts
3. Chondrocytes
1. Osteoprogenitor cells
2. Osteoblasts
3. Osteocytes
4. Osteoclasts
Development & Growth
Development & Growth
1. Chondrification (development)
2. Interstitial Growth (mass)
3. Appositional Growth (thickness)
1. Intramembranous Ossification
2. Endochondral Ossification
1. describe structure of bone (gross, histology, components)
2 describe bone formation cellular process (intracartilaginous ossification)
2.
3. describe bone growth, destruction of cartilage, ossification, remodelling
4. describe cells involved in bone dynamics (osteoblasts and osteoclasts)
Osteoblasts — form bone
Osteocytes — mature bone cells (enclosed)
Osteoclasts — break down bone
5. outline role of bone as a Ca2+ reservoir and outline its regulation
6. state the origin of new bone cells in growth and repair
Growth: ‘stem’ cells from ingrowth of CT and blood vessels
Repair: ‘stem’ cells in the periosteum
7. outline the hormonal regulation of serum calcium concentration
PTH (vital) — fall in [Ca2+], activates osteoclasts
Calcitonin (extreme demand) — rise in [Ca2+] inhibits osteoclasts.
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Lect 04 - Connective Tissue - Bone
Buzzwords - Cartilage
Perichondrium
G
Growth
th
Cartilage Types
Appositional
Interstitial
Hyaline cartilage
Elastic cartilage
Fibrocartilage
Articular Cartilage
Cells
Molecules
Glycosaminoglycans (GAGs)
Proteoglycan molecules
Buzzwords - Bone
Types of Bones
Functions of Bone
Cartilage components
Chondroblasts
Chondrocytes
1. Articular cartilage
2. Periosteum
Trabeculae
1. Osteoprogenitors
2. Osteoblasts
3. Osteocytes
4. Osteoclasts
Compact (cortical) bone
Cancellous (medullary) bone
6 zones of transition
Disease
Lacunae
Isogenous Group
Lamellae
Havers canal
Haversian systems
Volkmann’s canals
Lacunae
Canaliculi
Osteoid
Bone composition
Ground substance
Collagen Fibres
Elastic Fibres
Epiphysis
Diaphysis
Metaphysis
Osteoarthritis
Scurvy
1. Woven bone
2. Lamellar bone
Granulation
ranulation tissue
Provisional
rovisional callus
Bony
ony callus
Bony union
red marrow
yellow marrow
Appositional growth
Endochondral Ossification
Intramembranous Ossification
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