Reading: Ross and Pawlina Chapters 7 and 8; pages 198-209 and 218-243 (5th Ed.

pages: 182 - 237)

Cartilage:
Is a form of connective tissue composed of cells called chondrocytes and a highly

specialized extracellular matrix ( avascular) o Chondrocytes are sparsely distributed but essential in producing and maintaining the matrix
Hyaline cartilage distinguished by a homogenous, amorphous matrix o

Smooth (but not totally flat) bluish in color

Made up of mostly Type II collagen fibers, GAGs(LOTS), proteoglycans, and multiadhesive proteins.

o Articular cartilage ( no perichondrium), costal cartilages

Perichondrium separates dense connective tissue from the growing cartilage.

o Matrix is produced by chondrocytes and contains three major classes of molecules Highly hydrated to provide resilience and diffusion of small metabolites

o Chondrocytes are specialized cells that produce and maintain the extracellular matrix
o o

Components of the hyaline cartilage matrix are not uniformly distributed. Composition: Cells themselves are only 5% of cartilage tissue
60%-80% H2O ; 15% collagen II ; 10% proteoglycan, 5% multiadhesive glycoproteins; 5% chondroblasts, chondrocytes, fibroblasts (in fibrocartilage).

o Provides a model for developing skeleton of fetus o Firmly attached connective tissue, perichondrium, surrounds the hyaline cartilage o However, hyaline cartilage of articular joint surfaces do not possess a perichondrium.

 Elastic cartilage distinguished by presence of elastin in the cartilage matrix o

More flexible than hyaline ( and undinstiguishable from hyaline cartilage on H and E)need to do a special stain for elastic fibers, which stains them black.

o Made up of chondrocyte cells ( big, clear staining bubble appearance) surrounded by lots and lots of elastic fibers ( black staining hash-mark appearance)
o

Present in epiglottis, external ear , Eustachian tube

Fibrocartilage consists of chondrocytes and their matrix material in combination with

dense connective tissue ( NO Perchondrium)

o o

Transition Dense regular connective tissue and cartilage Cells reside in cavities called lacunae( the white spaces visible next to the nuclei are shaped like a new moon)

o Extracellular matrix of fibrocartilage is characterized by presence of both type I and II collagen fibrils
o

Annulus fibrosus(e.g. innervertebral disc), meniscus , tendons, ligaments

o Few isogenous groups interspersed with collagen fibers. o No perichondrium Chondrogenesis and Cartilage Growth: o Cartilage arises from mesenchyme during chondrogenesis o Cartilage is capable of two kinds of growth: appositional and interstitial Repair of Hyaline Cartilage: o Cartilage has limited ability for repair o When hyaline cartilage calcifies, its replaced by bone.

Bone:
Bone is a connective tissue characterized by mineralized (calcified) extracellular matrix

Cells associated with bone: o cartilage;

o

GFU granulocyte monocyte progenitor cell inactive osteoclasts active osteoclast ; mesenchymal stem cells osteoprogenitor cells osteoblasts osteocytes periosteal cells ( bone lining cells); endosteal cells;

Structure of Bone: o Epiphysis: ends of bones, usually made of cancellous (spongy) bone o Diaphysis: shaft of bone, usually made of lamellar (compact) bone o Compact= cortical =lamellar bone Channel along shaft of the bone has a marrow cavitiy at its center thats filled with red marrow Haversian canals ( vertical) and Volkmanns canals( horizontal) Periosteum membrane that covers the bone on the outside

Periosteum : seperates the bone from the outside, non-bone environment.

o

Outer (fibrous) layer made of dense irregular connective tissue (collagen fibers, fibroblasts, blood vessels, nerves..) Inner (cellular) layer made of periosteal(osteoprogenitor) cells Sharpeys fibers collagen fibers that extend into the bone tissue and are continuous with collagen fibers of extracellular matrix

Endosteum membrane that covers the bone on the inside, separating it from marrow cavities
o

One cell layer thick , consists of endosteal (osteoprogenitor) cells, the osteoblasts, and osteoclasts.

Lamella are layers of calcified fibrous tissue surrounding a central canal carrying an artery. The entire cylindrical unit is called the Haversian System or Osteon o Haversian canal is a channel down the center of each osteon that carries blood supply ( tiny arteries and veins) and nerves

o Spongy=cancellous bone Many, many trabecular that help distribute the load as force is applied to the bone at the joint. Area between trabeculae ( calcified portions) is filled with hemopoeitic tissue.

Functions :
Systems of levels that allows for movement Supports fleshy structures Protects vital organs Harbors bone marrow hemapoetic tissue produces WBC and RBC Reservoir of calcium, phosphate, etc.

Contains mainly type I collagen along with other matrix ( noncollagenous) proteins Bone matrix contains lacunae connected by network of canaliculi Bones and Bone tissue: o Classified as either Compact (dense) or Spongy (cancellous) o Classified according to shape; location of spongy and compact bone varies upon bone shape Outer surface of bones: o Bones are covered by periosteuma sheath of dense fibrous connective tissue containing osteoprogenitor cells o Bones that articulate with neighboring bones possess movable (synovial) joints. Bone Cavities: o Lined by endoosteumlayer of connective tissue cells that contain osteoprogenitor cells o Marrow cavity and the spaces in spongy bone contain bone marrow

 Mature bone: o Composed of structural units called osteons (Haversian systems) o Mature spongy bone is structurally similar to mature compact bone o Arteries that enter the marrow cavitiy through nutrient foramina supply blood to the shaft of long bones o Blood supply to bone tissue is essentially centrifugal Immature bone: o Forms more rapidly than mature bone. o Areas of immature bone are common in alveolar sockets of adult oral cavity and where tendons insert into bones. Cells of Bone tissue: o Osteoprogenitor cells : Osteoprogenitor cell is derived from mesenchymal stem cells Osteoprogenitor cell is resting cell that can differentiate into an osteoblast and secrete bone matrix

o Osteoblasts: Originates from mesenchymal stem cells. Responsible for synthesis of organic materials (25% of bone mass)

Type I collagen ( other collagen fibers are also produced)

Responsible for synthesis of ground substance

proteoglycans, multiadhesive glycoproteins Bone specific vitamin K-dependent, GFs

Plays an important role in deposition of inorganic matrix, calcium phosphate ( hydroxyapatite) 75% of bone mass Differentiated bone-forming cell that secretes bone matrix Osteoblast processes communicate with other osteoblasts and with osteocytes by gap junctions

Osteoblasts that become trapped in the bone matrix and remain isolated in lacunae become osteocytes

o Osteocytes: Mature bone cell enclosed by bone matrix that is previously secreted as an osteoblast

o Bone lining cells: Derived from osteoblasts and cover bone that is not remodeling.

o Osteoclasts:

Responsible for bone resorption Dervied from the fusion of mononuclear hemopeitic progenitor cells (CFU-GM) by expressing transcription factors and then RANK on developing oscteoclasts reacts with RANKL on stromal cells Large,multinucleated cell Acidophilic cytoplasm Microvillous-like border or ruffled border Clear zone, specialized attachment to matrix Found in a depression on the bone (Howships lacuna) Newly formed osteoclasts undergo an activation process to become bone-resorbing cells. Osteoclasts resorb bone tissue by releasing protons and lysosomal hydrolases into constricted microenvironment of extracellular space. Phagocytotic function of osteoclasts is regulated by many factors. The osteoclast dissolves the calcified structure of bone, absorbs the remnants up into the vesicles of the osteoclast cell, then returns the remnants (including Ca+) to the circulation for use elsewhere

o Canaliculi: Metabolites are unable to diffuse through calcified matrix of bone, the exchange between osteocytes and blood capillaries depends on communication through canaliculi

Exchange of nutrients and metabolites is a determing factor in the diameter of an osteon ( maximum number of lamellae: ~20)

Bone formation:

Development of bone is traditionally classified as endochondral or intermembranous but histologically, bone tissue is identical

o Intramembrane ossification:

Bone is formed by differentiation of mesenchymal cells into osteoblasts without involvement of cartilage. Newly formed bone matrix appears in histolofical sections as small, irregularly shaped spicules and trabeculae. Flatbones of skull, mandible, sternum, clavicle , scapula

Endochondral ossification: Rest of the bones in the body

Initially, hyaline cartilage model with the general shape of the bone is formed. Next hyaline cartilage is replaced by bone tissue. First sign of ossificationin is appearance of a cuff of bone around the cartilage model With establishment of periosteal bony collar, the chondrocytes in the midregion of cartilage model become hypertrophic. Calcified cartilage matrix inhibits diffusion of nutrients, causing death of chondrocytes in the cartilage model. Mesenchymal stem cells migrate into cavity along with growing blood vessels.

Growth of endochondral bone: o Endochondral bone growth begins in the second trimester of fetal life and continues into early adulthood o Growth in length of long bones depends on presence of epiphyseal cartilage
o

Bone deposition occurs on the cartilage spicules in the same manner as described for the formation of initial ossification center.

o Cartilage of epiphyseal growth plate is responsible for maintaining growth process

o When an individual achieves maximal growth, proliferation of new cartilage within epiphyseal plate terminates
o o

Bone tissue CANNOT grow interstitially by itself. With closure of epiphyseal plate, bone cannot grow in length and such individual is skeletally mature

o Bone increases in diameter by appositional growth, which is accomplished by addition of new bone to preexisting bony surface.
o

If bone growth continues in a skeletally mature person, this is called acromegaly

Bone remodeling o Osteoclast resportionosteoblast synthesis o Never stops bone appears to be stable but is rebuilding all the time due to recirculation of calcium and phosphate Equilibrium between removal and production determines bone density Osteoclasts remove osteons by dissolving them out, leaving a cutting cone. Osteoblasts lay down new bone matrix in the space left behind by osteocyte, thus closing the cone.

Bone Fracture
o

Granulation tissue formation of new loose,connective tissue, proliferation of capillatires and fibroblasts Soft callusremodeling of connective tissue into dense connective tissue and later into fibrous cartilage (hyaline) Bony callus formation of bone on basis of endochondral bone formation --cartilage is replaced by bone. Forming a callus

o Osteoclasts work through to remodel new bone at break site

o

Remodeling done by cutting and closing Surgical repair

Development of Osteonal (Haversian) System: o Osteons typically develop in pre-existing compact bone

o Durin development of new osteons, osteoclasts bore a tunnel, the resportion cavity, through compact bone. o Compact adult bone contains Haversian systems of varying age and size. Biologic mineralization and matrix vesicles o Biologic mineralization is a cell-regulated extracellular event o Mineraliation involves secretion of matrix vesicles into bony matrix Physiologic aspects of bone o Bone serves as a resoivor for body calcium o Bone can repair itself after injury