9.19.14 Bone & Cartilage

Long Bone: Structure

*Epiphyses*: 2 expanded ends of long bones; contain red bone marrow with developing blood cells; articular surface of epiphyses covered by *hyaline cartilage* *Epiphyseal Line*: (growth plate) formed by replacing the hyaline cartilage during growth; *separates epiphysis from metaphysis* *Diaphysis*: shaft of the long bone (thickness of the bone is compact) contains the *medullary cavity with marrow*. *Periosteum*: double layer of *dense irregular* *connective tissue*, covers the entire bone *except for joint surfaces*.

Hyaline Cartilag is a model for ?

the developing skeleton of fetus Calcified cartilage Is being replaced by bone here Hyaline cartilage- a precursor of bones that develop by the process of *endochondral ossification* -Cartilage is replaced by bone during development -Hyaline cartilage: *epiphyseal* (end of the bone) growth plate/disc: *disappears* when *bone growth is completed* *articular* cartilage (surface of epiphysis) contributes to synovial joint : remain throughout of life +*Continued proliferation of cartilage* leads to bone growth in length (cartilage calcification --> bone production and cartilage resorption)

Mature Bone: Osteons (Havasian systems)

*Haversian (osteon) System*: the basic unit of compact bone; consists of cylinder running parallel to the long axis of the bone. *Lamella*: concentric rings of the bony matrix forming the tubes. *Haversian (central) canal*: canal running through the middle of the Haversian system. containing blood vessels and nerve fibers. *Volkmanns' (perforating) canals*: run perpendicular to the long axis and provide channels for blood vessels and nerve fibers to connect adjacent Harversian systems.

Three types of cartilage

*Hyaline cartilage* (most prominent/common) & *Elastic cartilage* with elastic fibers common components: *chondroblasts and chondrocytes*; perichondrium, *type II* collagen and *PG aggrecan* *Fibrocartilage* components : chondroblasts , *fibroblasts*, *No perichondrium*, *type I* and type II collagen and *PG versican*

Fibrocartilage

*Resists deformation*, *compression* under stress; examples of location: *intervertebral discs*, symphysis pubis, *menisci* (knee joint), triangular fibrocartilage complex (wrist joint), insertion of tendons, etc Combination of *dense CT and hyaline cartilage*: contains *collagen I and II* -Contain chondrocytes and *fibroblasts* dispersed among collagen fibers -*Less matrix* than hyaline cartilage

What makes bone hard?

*hydroxyapatite crystals* mineralized matrix containing calcium phosphate -anchoring for muscles -protection of underlying organs -storage site for calcium and phosphate

Immature bone

-*Nonlamellar*- formed in the skeleton of a developing fetus does not have an organized lamellar organization -More cells *randomly arranged* -More *ground substance* (non-collagenous proteins) in matrix -Less mineralized

Types of bone tissue

-*compact (dense)* bone (*diaphysis of long bones and outer surface of flat bones*) -*spongy (cancellous)* bone (*interior* of long bones and flat bones) Bones-types: -Long; -Short -Flat -Irregular

Epiphyseal (secondary) ossification

-Growth in length of long bones depends on the presence of epiphyseal cartilage -As bones elongate, remodeling is required -When an individual achieves *maximal growth proliferation of new cartilage in the epiphyseal plate terminates*

Mature bone

-Outer *circumferential lamellae* -Cylindrical units (*osteons*) - *Haversian systems* with canals and lamellae -Inner circumferential lamellae -Bone matrix *contains lacunae* (cavity) with bone cells (osteocytes) -Lacunae are connected by *canaliculi* (processes in small tunnels)

Bone formation: Endochondral Ossification

1. From *mesenchyma*l cells a hyaline cartilage precursor is developed . 2. The cartilage model increases in size by *appositional and interstitial growth* 3. A bony collar is developed around the middle of the diaphysis when instead of chondroblasts being produced, osteoblasts are forming. 4. This *bone is formed intramembranously*, out of the periosteal tissue. 5. The bony collar *reduces diffusion of nutrients to the chondrocytes leading to their death*. 6. These *hypertrophic chondrocytes* synthesize *alkaline phosphatase* resulting in *calcification* of the cartilage matrix 7. As the chondrocytes die, the *osteoprogenitor cells migrate with the blood vessels*. 8. Osteoprogenitor cells contact the cartilaginous spicules and develop into osteoblasts which lay down osteoid

Long Bone: Spongy and Compact Tissues

Compact: dense layer forms outside of the bone Spongy: meshwork containing *trabeculae* ( thin anastomosing spicules) forms interior occupied by bone marrow Periosteum: *dense fibrous connective tissue* covers bones (except articular surface), contains *osteoprogenitor cells* - capable of growth *Endosteum*: connective tissue lining bone cavity (facing the bone *marrow cavity*) contains *osteoprogenitor cells*

Bone formation: Intramembranous ossification

Mesenchymal cells differentiate into osteoblasts. --> The osteoblasts secrete the bone matrix, osteoid. --> The bone expands by appositional growth. --> The bone spicules enlarge they become *interconected into a trabecular arrangement*

Chondrogenesis and Cartilage growth (2 types)

Most cartilage arises from *mesenchyme* during chondrogenesis -Cartilage : two kinds of growth -*interstitial* (Active during ossification) -*appositional* (new layer added to perichondrium surface) -*Damaged cartilage* -inability to heal due to avascularity and limited proliferation of mature chondrocytes -Some repair may only occur if the damage is at the *perichondrium*

Which bone cells known to actively synthesize the osteoid in a healthy individual?

Osteoblast Osteoblasts, cuboidal cell in the inside. mesenchymal is completely on the outside. http://www.youtube.com/watch?v=ymzkXget7R4 http://www.youtube.com/watch?v=rlesSq8m8JE

Bone remodeling by osteoclasts and osteoblasts

Osteoclasts migrate along bone deteriorating pits into the bone's surface, called *resorption bays*. Osteoblasts follow and lay new matrix. Bones that are under *constant stress remodel faster* than those that are not. osteoblasts are on the opposite side of osteoclasts

Cells of bone tissue

Osteogenesis: process of new bone formation Osteoprogenitor cells: flat shape, resting cell (external and internal surface of bone) derived from *mesenchymal stem cells in bone marrow*; can *differentiate to osteoblast*. Osteoblast: differentiated bone-forming cell; can divide; *secrets bone matrix- Collagen type I (90%)*, proteins and proteoglycans -forms osteoid (initial non-mineralized bone), responsible for calcification of bone matrix; communicate with other osteoblasts/osteocytes by gap junctions. -*active osteoblast-cuboidal shape*, -inactive osteoblast- *flat shape* Osteocyte: mature bone cell enclosed by bone matrix; *derived from osteoblast* after deposition of osteoid matrix; can synthesize new matrix, *do not divide*. Osteoclast: multinucleated cell, derived from fusion of mononuclear hemopoietic progenitor cells, responsible for *bone resorption*.

Osteons, osteocytes and canaliculi

The *system of canaliculi* serves for passage of substances between the osteocytes and blood vessels. Gap junctions are present at the contact parts of osteocyte processes. Osteoblast processes communicate with other osteoblasts and with osteocytes by *gap junctions*

ZONES of epiphyseal ossification

Vascular invasion zone --> hypertrophic zone (apoptosis of chondrocytes and calcification) --> Proliferating zone --> Reserve zone (growth in length) -- > epiphyseal cartilage (top)

Synovial joints

articular surface of neighboring bones are covered by *hyaline cartilage without perichondrium* has cavity, surrounded by ligaments and attached to tendons

Osteoporosis

can occur as a result of disease e.g., limb paralysis or prolonged bed rest. It results in increased tendency to *bone fracture* due to (*Thinner bone trabeculae* in osteoporosis ). It is common in post menopausal women. It results from higher activity of *osteoclasts*: resorption of bone exceeds deposition of bone.

chondrocytes produce matrix ___

collagen (*type II 80%*, other types 5-15 %: III, VI, IX, X, XI); GAGs (hyaluronan, chondroitin sulfate& keratan sulfate) form PG monomer- aggrecan-hyaluronan; mucoadhesive glycoproteins -*matrix (M)*-highly *hydrated* (water 60-80 %), diffusion of nutrients -regions of matrix: territorial (TM) and interrteritorial (IM) (between isogenic groups, darker stain with high sulfated PG) - *different concentration of sulfated PGs*

Bone formation order

intramembranous ossification, endochondral ossification- diaphysis (primary) and epiphysis (secondary

Paget's disease

of unknown cause. It results from *uncontrolled osteoclast activity*, leading to resorption of bone. Osteoblasts attempt to fill in the remaining erosions and continue to produce new bone to repair the damage. Thus paradoxically, the affected part of the *bone ends up larger* than it was originally. The repaired bone is less able to resist the physical stress and *more prone to fracture*.

Hyaline Cartilage

provides *cushioning*; exception: No perichondrium in *articular joints* 1. examples of location: epiphyseal plates, articular surface of synovial joints, costal cartilages of rib cage, larynx (thyroid, cricoid), rings of trachea, plates in bronchi etc. 2. composed of: *chondrocytes* (Ch) in *lacunae* (L), arranged in *isogenic groups* (cluster of chondrocytes in 2?) with capsular matrix (Cap- high concentration of *sulfated PGs*), perichondrium (P)

Elastic Cartilage

provides *flexible support*- contains *elastic fibers* examples of location: external ear, larynx (epiglottis), etc. It *does not calcify* during aging process

Osteoclasts

responsible for bone resorption -Active in bone remodeling and the *uptake of calcium to maintain calcium balance*. -The cells rest in a *depression called resorption bay (Howship's lacunae)* and posses a ruffled border. -Released into the lacunae are the *lysosomes which release hydrolytic enzymes to digest the matrix*. -Also released are *organic acids which lowers the pH and aids in decalcification* -Osteoclasts have *phagocytic functions* -Osteoclasts are more *numerous in sites where osteons* are being altered during growth -*Parathyroid hormone stimulates osteoclasts* and * calcitonin inhibits* them. -

Cartilage and Bone are ?

specialized connective tissue cartilage is *avascular* bone is *vascular*

Bone -structural support-

specialized connective tissue with *90 % of collagen (collagen type I main type* and small amount of collagen type V, III, XI) , GAGs, PGs, glycoproteins, growth factors and mineralized matrix containing calcium phosphate (form of *hydroxyapatite crystals*)

perichondrium

the *outer fibrous* layer: dense CT & fibroblasts, the *inner cellular* layer: chondroblasts gives rise to new cartilage cells (*appositional growth*). No perichondrium in *articular joints* of Hyaline cartilage only No perichondrium in fibrocartilage at all. allows for repair of cartilage in some cases