Cartilage and Bone

Question 1

General characteristics of cartilage

Answer 1

a. Origin. Cartilage is formed from mesenchyme during the 5th week of development.
b. Cartilage importance.
i. Cartilage is a specialized type of connective tissue, in which the consistency of the extracellular matrix allows the tissue to bear mechanical stress without permanent distortion. It provides firmness, elasticity, and tensile strength.
ii. Cartilage plays an important shock-absorbing function and forms smooth surfaces of synovial joints.
iii. Cartilage is a key tissue in the development of the fetal skeleton and most growing bones.
c. General features of the tissue.
i. Cartilage is avascular, so the nutrition of this tissue is by diffusion.
ii. Cartilage exhibits two types of growth: appositional (from the surface) and interstitial (from the inside).
iii. Cartilage has a poor ability for regeneration, which usually occurs through the formation of fibrous scar.

Question 2

Main components of cartilage

Answer 2

As any other connective tissue cartilage is composed of cells and extracellular matrix. Cartilage is usually covered with a connective tissue capsule called perichondrium.

Question 3

Perichondrium

Answer 3

composed of dense irregular connective tissue. Perichondrium allows passage for blood and lymphatic vessels and nerves.

Question 4

two main cells types that are found in the cartilage

Answer 4

chondroblasts and chondrocytes

Question 5

Chondroblasts

Answer 5

are found close to the surface of the cartilage and are derived from mesenchymal cells in the perichondrium. These cells are actively secreting cartilage matrix and have abundant RER and Golgi apparatus. Chondroblasts are responsible for the appositional growth of the cartilage

Question 6

Chondrocytes

Answer 6

are chondroblasts that became embedded in the cartilage matrix. The spaces in the matrix occupied by chondrocytes are called lacunae. Chondrocytes are specialized cells that produce and maintain the extracellular matrix. Chondrocytes are relatively large, rounded cells. They are capable of mitosis and are responsible for the interstitial growth of the cartilage. Dividing chondrocytes form clusters of cells called the isogenous groups.

Question 7

extracellular matrix of cartilage is composed of:

Answer 7

collagen, glycosaminoglycans, proteoglycans, and multiadhesive glycoproteins. The matrix is highly hydrated and consists of 60-70 % of water.

Question 8

Type II collagen

Answer 8

the principal type of collagen found in the cartilage matrix (except for fibrocartilage). It forms thin fibrils that are not visible in the light microscope, but show distinctive banding when viewed with an electron microscope. Collagen provides mechanical stability and tensile strength to cartilage.

Question 9

Glucosaminoglycans and proteoglycans

Answer 9

The ground substance of hyaline cartilage contains three main types of GAGs: hyaluronic acid, chondroitin sulfate, and keratan sulfate.

Question 10

Chondroitin sulfate and keratan sulfate

Answer 10

covalently linked to core proteins to form proteoglycans

Question 11

hyaluronic acid

Answer 11

bind non-covalently through a link protein to proteoglycans forming gigantic complexes. These complexes are carrying a large negative charge and bind water forming a hydrated gel.

Question 12

Multiadhesive glycoproteins

Answer 12

responsible for cross-linking collagen and proteoglycans and for attaching chondrocytes to the matrix.

Question 13

Histology of matrix

Answer 13

territorial- stains darker, richer in GAGs, fewer collagen

Interterritorial Matrix- in between lacunae, stains less intensely, not readily observed on all slides

Question 14

Hyaline cartilage

Answer 14

principal type of cartilage found in the body.

i. Hyaline cartilage has a well-developed perichondrium, composed of dense irregular connective tissue. Perichondrium is absent from the articular cartilages and epiphyseal plates.
ii. The matrix is composed primarily of collagen type II, GAGs, and proteoglycans. It does not contain fibers visible in a light microscope.
iii. Chondrocytes are located within the lacunae trapped in the matrix and are often arranged in isogenous groups.

Question 15

Location of hyaline cartilage

Answer 15

Hyaline cartilage is widely distributed in the body. It forms the embryonic skeleton and serves as a template for the bony skeleton. In adult humans, hyaline cartilage forms articular surfaces of most movable joints, epiphyseal plates, costal cartilages, and supports the respiratory system, where it is found in the nose, trachea, bronchi, and most of the larynx.

Question 16

Elastic cartilage

Answer 16

has a rather limited distribution.

i. Elastic cartilage has a well-developed perichondrium, similar to that of the hyaline cartilage.
ii. The matrix is composed primarily of collagen type II, GAGs, proteoglycans, and elastic fibers, that can be visible in a light microscope. The matrix of elastic cartilage does not ossify.
iii. Chondrocytes are located within large, distended lacunae.

Question 17

Location of elastic cartilage

Answer 17

Elastic cartilage is found in the ear auricle, external auditory canal walls, Eustachian tube, and epiglottis.

Question 18

Fibrocartilage

Answer 18

“hybrid” between hyaline cartilage and dense irregular connective tissue. Like elastic cartilage it has a rather limited distribution.

i. Fibrocartilage does not have a perichondrium.
ii. The matrix is composed of both collagen type II and type I, GAGs, and proteoglycans. The coarse fibers and bundles of collagen type I can be visualized in a light microscope.

Question 19

Location of fibrocartilage

Answer 19

found in intervertebral disks, pubic cartilage, and sternoclavicular and temporomandibular joints

Question 20

Cartilage pathologies

Answer 20

The malignant proliferation of cartilage is called chondrosarcoma. This cancer has a wide age range and has a slight male predominance. It can develop in any cartilage, but most commonly occurs in the pelvis, proximal femur, and proximal humerus. It is a slow growing tumor. Histologically, chondrosarcomas are composed of malignant cells with abundant cartilaginous matrix.

Question 21

General characteristics of bone

Answer 21

a. Bone is a connective tissue characterized by a mineralized extracellular matrix, which makes it one of the hardest tissues in the body. Like any other connective tissue, it is formed by collagen fibers, ground substance, and cells.
b. Bone is designed to withstand compression, deformation, and stress.
c. Because the extracellular matrix of bone is mineralized, the diffusion through this tissue is very limited, and bone, in contrast to cartilage, is a vascular tissue with blood and lymphatic vessels running through a system of canals

Question 22

Bone architecture

Answer 22

a. The outer rigid shell of the bone is formed by compact or cortical bone.
b. Spongy or trabecular bone forms series of spicules and trabeculae on the inner side of the compact bone that extend into the marrow cavity.
c. Marrow cavity is filled with reticular (hemopoietic) connective tissue or fat.
d. Bone coverings. The surface of bone is covered with a layer of connective tissue.
i. The external surface of the bone is covered with periosteum, which is a dense irregular connective tissue. Periosteum that covers an actively growing bone contains two layers, an external fibrous layer, which consists mainly of collagen fibers, and an internal osteogenic layer that contains osteoprogenitor cells.
ii. The internal (marrow cavity) surface of the bone is lined with endosteum, which is a thin layer of connective tissue with osteoprogenitor cells.

Question 23

Bone matrix

Answer 23

Unlike other connective tissues bone matrix includes two components, organic matrix and inorganic matrix.

Question 24

inorganic matrix

Answer 24

composed mostly of calcium phosphate (Ca(PO4)2) that exists mainly in the form of hydroxyapatite crystals (Ca10(PO4)6(OH)2). Other mineral components are present including calcium carbonate, Mg, Na, K, etc.

Question 25

Organic Matrix

Answer 25

a. similar to dense connective tissue in having large number of collagen type I bundles, GAGs, proteoglycans, and multiadhesive proteins. There is little ground substance in the bone matrix.
i. The major structural component of bone is type I collagen. Bundles of type I collagen give bone its tensile strength.
ii. GAGs, such as chondroitin sulfate and keratan sulfate, bind covalently to proteins to form large proteoglycan aggregates, which attach non-covalently to hyaluronic acid.
iii. Several multiadhesive glycoproteins are unique to the bone and are able to bind to both organic and inorganic components of the matrix.

Question 26

4 major bone cells

Answer 26

osteoprogenitor cells

osteoblast

osteocytes

osteoclasts

Question 27

Osteoprogenitor cells

Answer 27

found in periosteum and endosteum. They are derived from mesenchymal cells. Osteoprogenitor cells can differentiate into osteoblasts.

Question 28

Osteoblast

Answer 28

the principal bone-forming cell that secretes bone matrix. Osteoblasts are only found at the boundary between bone and adjacent tissue. Osteoblasts are versatile secretory cells. They secrete type I collagen and bone matrix proteins. They are also responsible for the calcification of the bone tissue as they lay down matrix vesicles. Osteoblasts secrete bone matrix onto the surface of the bone (appositional growth). Different from cartilage, bone can only grow appositionally due to the rigid calcified matrix. Active osteoblasts are cuboidal cells with basophilic cytoplasm and well-developed RER and Golgi apparatus. Inactive osteoblasts are squamous cells.

Question 29

Osteocytes

Answer 29

are osteoblasts that became trapped in the matrix. Osteocytes are housed in lacunae within the calcified bone matrix. Radiating out in all directions from the lacunae are narrow, tunnel-like spaces called canaliculi that connect adjacent lacunae. Canaliculi contain the osteocyte processes, which contact similar processes of neighboring cells and form gap junctions. Osteocytes are involved in the maintenance of bone and in deposition and mobilization of calcium from the matrix.

Question 30

Osteoclasts

Answer 30

large, multinucleated (up to 50 nuclei) cells with acidophilic cytoplasm. Osteoclasts are responsible for the resorption of bone. Osteoclast attaches to the bone via the actin-rich area called the clear zone. The part of the cell, which is in direct contact with the bone is called ruffled border and contains numerous plasma membrane infoldings. The osteoclast secretes H+ ions, collagenase, and other lysosomal enzymes into the pocket formed between the ruffled border and the bone surface promoting the local digestion of collagen and dissolving the calcium phosphate crystals. Depression in the matrix, etched by an osteoclast is called a Howship’s lacuna.

Question 31

Malignant proliferation of osteoblasts

Answer 31

characterized by the production of osteoid by malignant cells. It is the second most common primary malignancy of bone; osteosarcoma accounts for ~ 20% of primary bone cancers. Primary osteosarcomas occur most commonly in teenagers and occur at the sites of the most rapid bone growth, including the distal femur, proximal tibia, and proximal humerus. The high-grade osteosarcomas are highly metastatic.

Question 32

Osteoid osteoma

Answer 32

small benign tumor that occurs anywhere in the appendicular skeleton or the spine and causes acute night pains. Histologically the tumors are composed of primary bone with osteoblasts surrounding the osteoid.

Question 33

Paget’s disease

Answer 33

results in enlarged and deformed bones. It occurs in several stages. Initially there is an increased activity of osteoclasts that results in bone resorption, which is followed by the deposition of irregular patches of primary bone. The new bone is more fragile and is prone to fractures. The etiology of this disease is unknown.

Question 34

Primary or woven bone

Answer 34

the immature type of bone laid down either when the bones are first formed or during repair. The collagen fibers in this type of bone are irregular and interwoven.

Question 35

secondary or lamellar bone

Answer 35

the collagen fibers are organized into layers, or lamellae. This bone is much stronger than woven bone. The main structural unit of lamellar bone is an osteon.

Question 36

Osteon (or Haversian system)

Answer 36

concentric cylindrical structure formed around a central canal, which runs parallel to the long axis of the bone.

Question 37

Haversian canal

Answer 37

contains a neurovascular bundle surrounded by connective tissue. The Haversian canal is lined with osteoblasts, which separate the connective tissue from bone. The Haversian canal is surrounded by concentrically arranged lamellae. The collagen fibers within each lamella have the same orientation, while the fibers of the adjacent lamellae are at 90º to each other, so the structure of the mature bone has been likened to plywood.

Question 38

lacunae

Answer 38

osteocytes are located between the lamellae. The lacunae are connected by canaliculi.

Question 39

Volkmann’s canals

Answer 39

transverse channels in the mature bone through which blood vessels and nerves travel from the bone periphery to the Haversian canals; they also connect osteonal canals to one another. They usually run at approximately right angles to the long axis of osteons.

Question 40

Interstitial lamellae

Answer 40

represent the remnants of old Haversian systems, which have been partially obliterated by newly formed osteons.

Question 41

Outer circumferential lamellae

Answer 41

are laid down by osteoblasts formed from the periosteum on the outer side of the bone.

Question 42

Inner circumferential lamellae

Answer 42

are formed on the inner surface of the bone by osteoblasts derived from the endosteum.

Question 43

Bone remodeling

Answer 43

Bone is not a static tissue. It is being constantly remodeled. The old bone is removed by osteoclasts, and the osteoblasts lay down the new bone.

Question 44

Bone development and growth

Answer 44

Bone can form either by intramembranous ossification or by endochondral ossification.

Question 45

intramembranous ossification

Answer 45

bone is formed directly from connective tissue. Mesenchymal cells differentiate into osteoblasts, which start secreting bone matrix and form a network of spicules and trabeculae. This region of initial osteogenesis is called the primary ossification center. Osteoblasts that become trapped in the matrix become osteocytes. Most of the flat bones of the skull are formed this way.

Question 46

endochondral ossification

Answer 46

bone is formed by replacement of a cartilaginous template with bony tissue. Most of the long and short bones of the body are formed this way.

i. Endochondral ossification occurs in several phases: 1. First a miniature hyaline cartilage model is formed.
2. The cartilage model grows serving as a structural scaffold for bone development.
3. A cuff of bone is formed around the middle of the cartilage. The perichondrium in this part of the cartilage becomes invaded with blood vessels and turns into periosteum. At the end of this phase a bony collar is established around the diaphysis. The bony collar is formed by intramembranous ossification of the connective tissue.
4. With the development of the periosteal bony collar the chondrocytes in the midregion of the cartilage stop receiving nutrients, become hypertrophic, and the matrix around them becomes calcified.
5. The calcified cartilage matrix inhibits the diffusion of nutrients, causing death of chondrocytes in the cartilage model. 6. Blood vessels and osteoprogenitor cells migrate into the degenerated cartilage.
7. Osteoprogenitor cells differentiate into osteoblasts, which line up on the surface of calcified cartilage and start secreting bone matrix.
8. Remodeling of newly synthesized bone and underlying calcified cartilage results in the replacement of calcified cartilage by bone matrix.

Question 47

Ossification of long bones.

Answer 47

1. The primary ossification center is located in the diaphysis of a long bone.
2. The secondary ossification centers are located in the epiphyses of long bones. Secondary ossification centers are responsible for the formation of the articular cartilage and the epiphyseal or growth plate, which connects each epiphysis to the diaphysis. The epiphyseal plate is responsible for the bone growth and disappears in adults. The epiphyseal plate can be divided into five zones: a. Zone of reserve cartilage consists of regular hyaline cartilage with typical chondrocytes.
   b. Zone of proliferation is characterized by the rapid tissue growth and division of chondrocytes, which form columns of stacked cells (isogenous groups), which are parallel to the long axis of the bone.
   c. Zone of hypertrophy contains swollen chondrocytes, whose cytoplasm contains much glycogen. Hypertrophy of chondrocytes and the increase in the size of lacunae causes the compression of the matrix into thin septa.
   d. In the zone of calcification the chondrocytes are lost by apoptosis, which is accompanied by the calcification of cartilage matrix.
   e. Zone of ossification is characterized by the appearance of bone tissue, which is synthesized by osteoblasts over the layer of calcified cartilage.