Bone Tissue• Main Features:

– Vascular with Nerve Supply.

– Full power of Regeneration.

– Undergoes Continuous Remodeling

Functions of Bones

1. Solid Support.

2. Storage of Minerals; Calcium (Circulates)

3. Blood Cells Production.

4. Leverage of Motion

5. Protection, Skull:-Brain, Chest Wall:-Heart &

Lungs. Pelvis:- Uterus & Urinary bladder

2

Structure of Long Bone

• Long bones consist of a diaphysis and an

epiphysis

• Diaphysis

– Tubular shaft that forms the axis of long

bones

– Composed of compact bone that surrounds

the medullary cavity

– Yellow bone marrow (fat) is contained in the

medullary cavity

3

Structure of Long Bone

• Epiphyses

– Expanded ends of long bones

– Exterior is compact bone, and the interior is

spongy bone

– Joint surface is covered with articular

(hyaline) cartilage

– Epiphyseal line separates the diaphysis from

the epiphyses

Long Bones – Femur (ex)

Figure 6–2a

• Diaphysis - the shaft – A heavy wall of compact bone, or dense bone

– A central space called marrow cavity

• Epiphysis- wide part at each

end & articulation with other

bones

– Mostly spongy (cancellous) bone

– Covered with compact bone

(cortex)

• Metaphysis:

–where diaphysis and epiphysis meet

5

Structure of Long Bone

Figure 6.3

Mesenchymal cells

• During development, Mesenchymal

Cells give rise to other cell types of the

connective tissue. They are the

Multipotent Stem cells that can

differentiate and give rise to different CT-

cells as Fibroblast, chondroblast and

osteoblasts. Mesenchymal cells are

smaller than fibrocytes and difficult to

detect in histological sections.

Formation of CTs

• Blast Cells of CT & Derivatives (Bone,

Cartilages Secret Extracelluar

Matrix & Fibers

• Then called Cytes.

• Fibroblast Fibrocyte

• Chondroblast Chondrocyte

• Osteoblast Osteocyte

Connective Tissue

•Structure:

•1. Cells2. Extracelluar

Matrix 3. Fibers

•Cells are derived from

Mesenchymal Tissue

•Immature Cell (Mitosis)

called Blasts as fibroblast,

Osteoblast & Chondroblast

•The surrounding where

cells & fibers are Present is

called Extracellular Matrix

3. Osteoprogenitor Cells

• Are located in inner, cellular layer of

periosteum (endosteum).

• Assist in fracture repair

• Mesenchymal stem cells that divide to produce osteoblasts

10

Bone Membranes• Periosteum – double-layered protective

membrane– Outer fibrous layer is dense regular connective

tissue

– Inner osteogenic layer is composed of osteoblasts and osteoclasts

– Richly supplied with nerve fibers, blood, and lymphatic vessels, which enter the bone via nutrient foramina

– Secured to underlying bone by Sharpey’s fibers

• Endosteum – delicate membrane covering internal surfaces of bone

Bone Cells

• Osteoprogenitor cells (or stem cells of bone)– are located in the periosteum and endosteum. They

are very difficult to distinguish from the surrounding connective tissue cells. They differentiate into

• Osteoblasts (or bone forming cells). – Osteoblasts may form a low columnar "epitheloid

layer" at sites of bone deposition. They contain plenty of rough endoplasmatic reticulum (collagen synthesis) and a large Golgi apparatus. As they become trapped in the forming bone they differentiate into

• Osteocytes. – Osteocytes contain less endoplasmatic reticulum and

are somewhat smaller than osteoblasts.

Bone Cells

Figure 6–3 (1 of 4)

Osteocytes: Mature bone cells that

maintain the bone matrix

• Live in lacunae

• Are between layers (lamellae) of

matrix

• Connect by cytoplasmic extensions

Through Canaliculi in lamellae. Gap

Junctions (Ionic + Nutrients)

• Do not divide but Recruit Osteoblast

• Maintains protein and mineral content

of matrix.

• Produce factors that respond to Stress

In Bones.

Osteocytes

• Respond To Tension placed on bones Secret

cAMP, Osteclacin and growth factors…..

Hence Recruit Osteoblasts to form new bone

Tissue.

• The Space between Osteocyte membrane

and Canaliculi/Wall of Lacunae called

Periosteocytic Space containing Bony

Fluid of about 1.3 L. Function as Route of

Calcium circulation during bone formation &

Transmits Mechanical Stress between

Osteocytes & Osteoblasts

2. Osteoblasts• Immature Bone Cells that

secrete matrix compounds

(osteogenesis)

• Extracellular Matrix: Two

Units:

• 1. Organic Matrix: Osteoid

–produced by osteoblasts,

but not yet calcified to

form bone

• 2. Inorganic Matrix:

Osteon: Mineralized bone

tissue

Osteoclasts

• are very large (up to 100 µm), Multi-nucleated

(about 5-10 visible in a histological section, but

up to 50 in the actual cell) Bone-resorbing

Cells. They arise by the fusion of Monocytes

(macrophage precursors in the blood) or

macrophages. Osteoclasts attach themselves

to the bone matrix and form a tight seal at the

rim of the attachment site.

Osteoclast

Osteoclasts

• invaginations forming a Ruffled Border. Osteoclasts empty the contents of Secretions (Acidphophotase, Proteinase & lysosomes) into the extracellular space between the ruffled border and the bone matrix. The released enzymes Break Down The Collagen Fibres of the matrix. Osteoclasts are Stimulated By Parathyroid Hormone (produced by the parathyroid gland) and inhibited by Calcitonin (produced by specialised cells of the thyroid gland). Osteoclasts are often seen within the indentations of the bone matrix that are formed by their activity (resorption bays or Howship's lacunae).

• Pump Hydrogen Ions and Chloride so decrease the PH, hence Acidic and that digest the dying bone matrix

• Differentiate from mononuclear origin Via Three Signaling

Molecules Secreted By Osteoblasts:

• 1. Macrophage colony-stimulating factor (M-

CSF). It binds to a receptor on Macrophage and it

induces expression of receptor for the activation of

Nuclear Factor Kappa (RANK).

• The second Signaling molecule is

RANKL(Ligand) Induces the expression of

multinucleated Osteoclast.

• The Third Signaling factor is Osteoprotegerin (OPG)

binds to macrophage and inhibiting its transformation into

an Osteoclast (Regulation). Inhibits Osteoclast

Differentiation, Fusion, And Activation

Osteoclast Formation

Bone Matrix• Consists of two parts:

• 1 Organic Matrix: Secreted initially while

forming the primary bone (Osteoid).

• 2 Inorganic part: Made of Minerals.

• Initially, Osteoblasts lay down the organic

matrix and collagen in Irregular Fashion.

• Later-on, collagen is arranged in

lamellae (Layers around the central

Haversian canal

Bone Matrix

• Bone matrix consists of collagen fibres (about 90% of the organic substance) and Ground Substance. Collagen type I is the dominant collagen form in bone. The hardness of the matrix is due to its content of inorganic salts (hydroxyapatite; about 75% of the dry weight of bone), which become deposited between collagen fibres.

• Calcification begins a few days after the deposition of organic bone substance (or osteoid) by the osteoblasts. Osteoblasts are capable of producing high local concentration of Calcium Phosphate in the extracellular space, Which Precipitates On The Collagen Molecules. About 75% of the hydroxyapatite is deposited in the first few days of the process, but complete calcification may take several months.

Bone Matrix, Organic Part

• Proteoglycans noncovalently linked to

Hyaluronic acid form very Large

Aggrecan Complex.

• Osteoclacin: Binds to Hydroxyapatite

leading to Mineralization.

• Osteopontin: Binds to Hydroxyapatite and

integrins on Osteoblasts and Osteoclasts

(Sealing).

• Sialoprotein: Binding Osteoblast to matrix

Composition of Bone: Matrix

• Cortical/

Compact

Bone

• Cancellous/

Trabecular/

Spongy Bone

Histological Organization of Bone

• Compact Bone

• Compact bone consists mainly of extracellular

substance matrix. Osteoblasts deposit the matrix in

the form of thin Sheets which are called lamellae.

Lamellae are microscopical structures. Collagen

fibres within each lamella run parallel to each other.

Collagen fibres which belong to adjacent lamellae run

at oblique angles to each other.

• Bone which is composed by lamellae when viewed

under the microscope is also called Lamellar Bone.

Histological Organisation of Bone

Histological Organization of Bone

• In the process of the deposition of the matrix, Osteoblasts become encased in small hollows within the matrix, the Lacunae. Unlike chondrocytes, osteocytes have several thin processes; Canaliculi. They extend from the lacunae into small channels within the bone matrix , the Canaliculi arising from one lacuna may Anastomose with those of other lacunae and, eventually, with larger, vessel-containing canals within the bone.

• Canaliculi provide the means for the osteocytes to communicate with each other and to exchange substances by diffusion. Very Important create passage of factors that communicate Osteocyts with Osteoblast to Transmit Infos about stress on bone hence adaptation

Histological Organisation of Bone

29

Microscopic Structure of Bone:

Compact Bone• Haversian system, or osteon – the

structural unit of compact bone

– Lamella – weight-bearing, column-like matrix

tubes composed mainly of collagen

– Haversian, or central canal – central channel

containing blood vessels and nerves

– Volkmann’s canals – channels lying at right

angles to the central canal, connecting blood

and nerve supply of the periosteum to that of

the Haversian canal

Histological Organisation of Bone

Histological Organization of Bone

• In mature compact bone most of the individual

lamellae form concentric rings around larger

longitudinal canals (approx. 50 µm in

diameter) within the bone tissue. These canals

are called Haversian canals. Haversian canals

typically run parallel to the surface and along

the long axis of the bone. The canals and the

surrounding lamellae (8-15) are called a

Haversian system or an osteon. A Haversian

canal generally contains one Or Two

Capillaries And Some Nerve Fibres.

1. Compact Bone

Figure 6–5

Bone Tissues - 2

Osteon• The basic unit

of mature compact bone

• Osteocytes are arranged in concentric lamellae

• Around a central canal containing blood vessels

Perforating Canals• Perpendicular to

the central canal

• Carry blood

vessels into bone

and marrow

Circumferential

Lamellae• Lamellae

wrapped

around the

long bone

• Binds osteons

together

•Compact bone is covered with membrane:

– periosteum - outside & endosteum - inside

Periosteum• Covers all bones except parts

enclosed in Joint Capsules

• It is made up of an outer, fibrous

layer and an inner, cellular layer

Functions of Periosteum1. Isolate bone from surrounding

tissues

2. Provide a route for circulatory

and nervous supply

3. Participate in bone Growth And

Repair

Compact Vs. Spongy

•

Bone Development

• Osteogenesis and ossification – the

process of bone tissue formation, which

leads to:

– The Formation Of The Bony Skeleton In

Embryos

– Bone Growth Until Early Adulthood

– Bone Thickness, Remodeling, And Repair

Formation of the Bony Skeleton

• Begins at Week 8 of embryo development

• Intramembranous ossification – bone

develops from a fibrous membrane. All

Flat Bones Develop via this method (skull

and the clavicles

• Endochondral ossification – bone forms by

replacing hyaline cartilage. All Long &

Irregular Bones develop via this method (

Stages of Intramembranous

Ossification• An ossification center appears in the

fibrous connective tissue membrane

• Bone matrix is secreted within the fibrous

membrane

• Woven bone and periosteum form

• Bone Collar (Primary Bone-Woven

Form; Collagen Not Lamellated) of

compact bone forms, and red marrow

appears

Formation of Bone

• Bones are formed by two mechanisms:

• Intramembranous ossification (bones of the skull, part of the mandible and clavicle) .

• Intramembranous Ossification: Occurs within a membranous, condensed plate of mesenchymal cells. At the initial site of ossification (ossification centre) mesenchymal cells (osteoprogenitor cells) differentiate into osteoblasts. The osteoblasts begin to deposit the organic bone matrix, the osteoid.

• The matrix separates osteoblasts, which, from now on, are located in lacunae within the matrix. The collagen fibres of the osteoid form a woven network without a preferred orientation, and lamellae are not present at this stage. Because of the lack of a preferred orientation of the collagen fibres in the matrix, this type of bone is also called woven bone. The osteoid calcifies leading to the formation of primitive trabecular bone.

Intramembranous Ossification

41

Stages of Intramembranous

Ossification

Figure 6.7.1

42

Stages of Intramembranous

Ossification

Figure 6.7.2

43

Stages of Intramembranous

Ossification

Figure 6.7.3

44

Stages of Intramembranous

Ossification

Figure 6.7.4

Postnatal Bone Growth• Growth In Length Of Long Bones

– Cartilage on the side of the epiphyseal

plate closest to the epiphysis is relatively

inactive

– Cartilage adjacent to the shaft of the bone

organizes into a pattern that allows fast,

efficient growth

– Cells of the epiphyseal plate proximal to the

resting cartilage form three functionally

different zones: Division, hypertrophy, and

osteogenic phases

Endochondral Ossification

• Most bones are formed by the transformation of cartilage "bone models", a process called Endochondral Ossification. A periosteal budinvades the cartilage model and allows osteoprogenitor cells to enter the cartilage. At these sites, the cartilage is in a state of hypertrophy (very large lacunae and chondrocytes) and partial calcification, which eventually leads to the death of the chondrocytes.Invading osteoprogenitor cells mature into osteoblasts, which use the framework of calcified cartilage to deposit new bone. The bone deposited onto the cartilage scaffold is lamellar bone. The initial site of bone deposition is called a primary ossification centre. Secondary ossification centres occur in the future epiphyses of the bone.

Endochondral Ossification

• A thin sheet of bone, the periosteal collar, is deposited around the shaft of the cartilage model. The periosteal collar consists of woven bone.

• Close to the zone of ossification, the cartilage can usually be divided into a number of distinct zones :

• Reserve Cartilage, furthest away from the zone of ossification, looks like immature hyaline cartilage.

• A zone of Chondrocyte Proliferation contains longitudinal columns of mitotically active chondrocytes, which grow in size

• the zone of Cartilage Maturation And Hypertrophy.

• A zone of Cartilage Calcification forms the border between cartilage and the zone of bone deposition.

Stages of Endochondral Ossification

• 1. Formation Of Bone Collar

• 2. Cavitation Of The Hyaline Cartilage

• 3. Invasion Of Internal Cavities By The

Periosteal Bud, And Spongy Bone

Formation

• 4. Formation Of The Medullary Cavity;

• 5. Appearance Of Secondary Ossification

Centers In The Epiphyses

• 6. Ossification Of The Epiphyses, With

Hyaline Cartilage Remaining Only In The

Epiphyseal Plates

49

Formation

of bone

collar

around

hyaline

cartilage

model.

1

2

3

4

Cavitation

of the

hyaline

cartilage

within the

cartilage

model.

Invasion of

internal cavities

by the

periosteal bud

and spongy

bone formation.

5 Ossification of the

epiphyses; when

completed, hyaline

cartilage remains

only in the

epiphyseal plates

and articular

cartilages

Formation of the

medullary cavity as

ossification continues;

appearance of

secondary ossification

centers in the

epiphyses in

preparation for stage 5.

Hyaline

cartilage

Primary

ossification

center

Bone

collar

Deteriorating

cartilage matrix

Spongy

bone

formation

Blood

vessel of

periostea

l bud

Secondary

ossification

center

Epiphyseal

blood vessel

Medullary

cavity

Epiphyseal

plate

cartilage

Spongy

bone

Articular

cartilage

Stages of Endochondral Ossification

Figure 6.8

Endochondrial Ossification

Bone Growth

• Changes in the size and shape of bones

during the period of growth imply some

bone reorganization. Osteoblast and

osteoclast constantly deposit and remove

bone to adjust its properties to growth-

related demands on size and/or changes

of tensile and compressive forces

Bone Remodeling:

Reorganisation and Restoration of Bone

Bone Remodeling• Bone structural integrity is continually

maintained by remodeling

– Osteoclasts and osteoblasts assemble into Basic Multicellular Units (BMUs)

– Bone is completely remodeled in approximately 3 years

– Amount of Old Bone Removed Equals New Bone Formed

BMU Remodeling Sequence

Activation

Resorption

Reversal

Quiescence

Formation &

Mineralization

www.ifcc.org/ejifcc/ vol13no4/130401004n.htm

Osteocytes

• Reorganization of bone may continue throughout life to mend damage to bone (e.g. microfractures) and to counteract the wear and tear occurring in bone. Osteoclasts and osteoblasts remain the key players in this process. Osteoclasts "drill" more or less circular tunnels within existing bone matrix. Osteoblasts deposit new lamellae of bone matrix on the walls of these tunnels resulting in the formation of a new Haversian system within the matrix of compact bone. Parts of older Haversian systems, which may remain between the new ones, represent the interstitial lamellae in mature bone. Capillaries and nerves sprout into new Haversian canals.

Reorganization and Restoration of Bone

Reorganisation and Restoration of Bone

• Restorative activity continues in aged humans (about 2% of the Haversian systems seen in an 84 year old individual contained lamellae that had been formed within 2 weeks prior to death!). However, the Haversian systems tend to be smaller in older individuals and the canals are larger because of slower bone deposition. If these age-related changes in the appearance of the Haversian systems are pronounced they are termed osteopeniaor senile osteoporosis. The reduced strength of bone affected by osteoporosis will increase the likelihood of fractures.

Hormonal Mechanism

• Rising blood Ca2+ levels trigger the thyroid to

Release Calcitonin

• Calcitonin stimulates calcium salt deposit in

bone

• Falling blood Ca2+ levels signal the

parathyroid glands to release PTH

• PTH signals osteoclasts to degrade bone

matrix and release Ca2+ into the blood

58

Hormonal Mechanism

Figure 6.12

Response to Mechanical Stress

• Wolff’s law – a bone grows or remodels in

response to the forces or demands placed

upon it

• Observations supporting Wolff’s law include

– Long bones are thickest midway along the shaft

(where bending stress is greatest)

– Curved bones are thickest where they are most

likely to Bend

Response to Mechanical Stress

• Trabeculae form along lines of stress

• Large, bony projections occur where heavy,

active muscles attach.

• Un Opposed Teeth Will Grow Longer.

• Orthodontics: The Principal ??

61

Response to Mechanical Stress

Figure 6.13

Clinical Application• Changes with Age:

• Periosteal bone Remodeling Exceeds that of

Endosteal Type; Hence The Bone Widens more

hence the person get Shorter as they age.

• Post- Menopuase Changes:

• Decrease Estrogen leas to Decrease Calcium

Absorption Hence Bone Resoprption more than

Repair; Osteoporosis.

• Diseases that Affect Collagen

Orthodontics: Walking Teeth

Before & After