Cartilage-and-bone - Chapter summary for Cartilage and bone - Junqueira\'s Basic Histology PDF

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Summary

Cartilage and bone Endochondral bone formation o Long bones formed in the embryo as cartilage, act as a template that is later replaced by bone.  Intramembranous bone formation o Flat bones formed within preexisting membranous sheath.Cartilage Possesses cells known as chondrocytes o Occupy small ...

Description

Cartilage and bone 

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Endochondral bone formation o Long bones formed in the embryo as cartilage, act as a template that is later replaced by bone. Intramembranous bone formation o Flat bones formed within preexisting membranous sheath.

Cartilage 

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Possesses cells known as chondrocytes o Occupy small cavities (lacunae) within the extracellular matrix  Secreted by chondrocytes  Composed of glycosaminoglycans and proteoglycans Neither vascularized, supplied with nerves nor lymphatic vessels. o Receive nourishment from blood vessels of surrounding connective tissues by diffusion. 3 types of cartilage according to the fibers present in the matrix o Hyaline cartilage  Contain type II collagen in its matrix  Most abundant in the body o Elastic cartilage  Contain type II collagen + elastic fibers o Fibrocartilage  Contain type I collagen Perichondrium: connective tissue sheath covering most cartilage o Has 2 layers  Outer fibrous layer  Inner cellular layer  Secrete cartilage matrix o Vascular o Absent in fibrocartilage o Areas where cartilage has no perichondrium  The articular surface of the bones forming a joint  Receive their nourishment from the synovial fluid

Hyaline cartilage Hyaline cartilage, the most abundant cartilage in the body, forms the template for endochondral bone formation.  Locations o Nose and larynx o Ventral ends of the ribs where they articulate with the sternum o Tracheal rings and bronchi o Articulating surfaces of the movable joints of the body  Form cartilage template for many bones during embryonic development  Constitutes the epiphyseal plates of growing bones

Histogenesis and growth of hyaline cartilage Cells responsible for hyaline cartilage formation differentiate from mesenchymal cells.  Interstitial growth o Mesenchymal cells congregate in dense masses called chondrification centers  Differentiate into chondroblasts  Secrete the typical cartilage matrix  Become entrapped in small individual compartments, lacunae o Chondroblasts become known as chondrocytes  Capable of cell division  Form isogenous groups o Manufacture matrix and become surrounded by their own lacunae  Lead to cartilage growth. o Occur only in the early phase of hyaline cartilage formation o Articular cartilage lacks perichondrium and increases in size only by interstitial growth. o Occurs in the epiphyseal plates of long bones  Lacunae are arranged in longitudinal orientation  Lengthen the bone  Appositional growth o Mesenchymal at the periphery of the developing cartilage differentiate to form chondroblasts  Form perichondrium  Dense irregular collagenous connective tissue  Responsible for the growth and maintenance of cartilage  Has 2 layers o Outer fibrous layer  Type I collagen  Fibroblasts  Blood vessels o Inner cellular layer  Chondrogenic cells  Differentiate into chondroblasts o Secrete matrix which lead to cartilage growth at the periphery  Chondroblasts removed from their matrix o Cease to secrete cartilage matrix containing type II collagen o Become fibroblasts like and start secreting type I collagen

Cartilage cells 

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Chondrogenic cells o Derived from mesenchymal cells o Can differentiate into chondroblasts and osteoprogenitor cells Chondroblasts o Derived from 2 sources  Mesenchymal cells in chondrification centers  Chondrogenic cells of inner cellular layer of perichondrium (appositional growth) Chondrocytes o Are chondroblasts that are surrounded by matrix o Ovoid at the periphery and round deeper

Matrix of hyaline cartilage The matrix of hyaline cartilage is composed of type II collagen, proteoglycans, glycoproteins and extracellular fluid.  Contain 40% collagen  Contain type II collagen but also type IX, X and XI  Divided into 2 regions o Territorial matrix  Poor in collagen  Rich in chondroitin sulfate o Interterritorial matrix  Rich in type II collagen  Poor in proteoglycans  Pericellular capsule: small region of the matrix, immediately surrounding the lacuna o Protect chondrocytes from mechanical stresses  Rich in aggrecans o Large proteoglycan molecules composed of protein core to which glycosaminoglycans are covalently linked o Noncovalently linked to hyaluronic acid forming huge aggrecan composites o Their abundant negative charge attract cations, Na+ ions  Attract water molecules  Contain adhesive glycoprotein, chondronectin o Similar to fibronectin o Has binding site for  Type II collagen  Chondroitin 4-sulfate  Chondroitin 6-sulfate  Hyaluronic acid  Integrins (transmembrane proteins) of chondroblasts and chondrocytes

Clinical correlations 

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Hyaline cartilage degenerates when the chondrocytes hypertrophy and die and the matrix begins to calcify o Integral part of endochondral bone formation o Natural process of aging  Result in less mobility and in joint pain Chondrogenic cells from the perichondrium enter the defect and form new cartilage o Form connective tissue in large defect

Effects of hormones and vitamins on hyaline cartilage 

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Hormones o Thyroxine + testosterone + somatotropin (via insulin-like growth factor)  Stimulate cartilage growth and matrix formation o Cortisone + hydrocortisone + estradiol  Inhibit cartilage growth and matrix formation Vitamins o Hypovitaminosis A  Reduces width of epiphyseal plates o Hypervitaminosis A  Accelerates ossification of epiphyseal plates o Hypovitaminosis C  Inhibits matrix synthesis  Deforms architecture of epiphyseal plate,

 Lead to scurvy o Absence of vitamin D  Result in deficiency in absorption of calcium and phosphorus  Proliferation of chondrocytes is normal  Matrix does not become calcified properly  Result in rickets

Elastic cartilage Elastic cartilage greatly resembles hyaline cartilage, except that its matrix and perichondrium possess elastic fibers.  Locations o Pinna of the ear o External and internal auditory tubes o Epiglottis o Larynx (cuneiform cartilage)  Has more chondrocytes than hyaline cartilage

Fibrocartilage Fibrocartilage, unlike hyaline and elastic cartilage, does not possess a perichondrium and its matrix includes type I collagen.  Locations o Intervertebral discs  Interposed between the hyaline cartilage coverings of the articular surface of the vertebrae  Contain a gelatinous center, nucleus pulposus  Composed of cells derived from notochord lying within hyaluronic acid-rich matrix o Disappear by age 20 year  Surrounded by annulus fibrosus o Layer of fibrocartilage with type I collagen o Pubic symphysis o Articular discs o Attached to bone  Does not possess perichondrium  Contain bundles of type I collagen  Its chondrocytes arise from fibroblasts

Clinical correlations 

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Ruptured disc o Caused by tear or break in the laminae of the annulus fibrosus through which the gel-like nucleus pulposus extrudes  Occur on the posterior portion of the intervertebral discs  In lumbar region Achondroplasia o Dwarfism  Caused by a mutation encoding for fibroblast growth factor FGFR3

Bone Bone is specialized connective tissue whose extracellular matrix is calcified, incarcerating the cells that secreted it.  Stores 99% of the body’s calcium  Contain a central cavity, marrow cavity o Houses the bone marrow (hemopoietic organ) o Lined with endosteum  Specialized thin connective tissue  Composed of  Osteoprogenitor cells  Osteoblasts  Covered on its external surface with periosteum (except at synovial articulation) o Outer layer of dense fibrous connective tissue o Inner cellular layer  Osteoprogenitor (osteogenic) cells  Composed of cells lying in an extracellular matrix that has become calcified o Fibers  Type I collagen o Ground substance  Proteoglycans  Chondroitin sulfate  Keratan sulfate  Glycoproteins  Osteonectin  Osteocalcin  Osteopontin  Bone sialoprotein  Cells of bone o Osteoprogenitor cells  Differentiate into osteoblasts  Responsible for secreting the matrix  Known as osteocytes when surrounded by matrix (occupy lacunae) o Osteoclasts  Multinucleated cells  Derived from fused bone marrow precursors  Responsible for bone resorption and remodeling  Methods of preparing bone for studying o Decalcified sections  Decalcifying the bone in an acid solution to remove calcium salts  Tissue is then embedded, sectioned and routinely stained for study  Disadvantages  Osteocytes are distorted by the decalcifying acid bath o Ground sections  Sawing the bone into thin slices  Grinding the sections with abrasives between glass plates  When the section is sufficiently thin for study with light microscope  Disadvantages  Cells are destroyed  Lacunae and canaliculi are filled in with bone debris

Bone matrix Inorganic component The inorganic constituents of bone are crystals of calcium hydroxyapatite, composed mostly of calcium and phosphorous.  Constitute 65% of bone dry weight  Composed of o Calcium o Phosphorus o Bicarbonate o Citrate o Magnesium o Sodium o Potassium  Calcium and phosphorus exist in the form of hydroxyapatite crystals o Its surface ions attract H2O and form a hydration shell  Permits ion exchange with the extracellular fluid  Bone is one of the hardest substances in the body o Its hardness is due to the association of hydroxyapatite crystals with collagen  If bone is decalcified (mineral is removed), it still retain its original shape but becomes flexible  If the organic component is removed, it becomes extremely brittle than can be fractured with ease.

Organic component The predominant organic component of bone is type I collagen.  Type I collagen  Glycoproteins o Osteocalcin  Bind to hydroxyapatite o Osteopontin  Bind to hydroxyapatite  Bind to integrins on osteoblasts and osteoclasts o Bone sialoprotein  Bind to matrix components  Bind to integrins of osteoblasts and osteocytes  Vitamin D stimulates synthesis of glycoproteins

Cells of Bone Osteoprogenitor cells Osteoprogenitor cells are derived from embryonic mesenchymal cells and retain their ability to undergo mitosis.  Locations o Inner cellular layer of periosteum o Lining haversian canals o Endosteum  Derived from embryonic mesenchyme  Remain in place throughout postnatal life  Can undergo mitotic division  Can differentiate into osteoblasts  May differentiate into chondrogenic cells under conditions of low oxygen tension  Active during the period of intense bone growth

Osteoblasts Osteoblasts not only synthesize the organic matrix of bone but also possess receptors for parathyroid hormone.  Derived from osteoprogenitor cells  Develop under the influence of o Bone morphogenic protein (BMP) family o Transforming growth factor-B  Synthesize organic protein components of the bone matrix o Type I collagen o Proteoglycans o Glycoproteins  Produce o RANKL  Receptor for activation of nuclear factor kappa B o Osteocalcin  For bone mineralization o Osteopontin  For formation of sealing zone between osteoclasts and the subosteoclastic compartment o Osteonectin  Related to bone mineralization o Bone sialoprotein  Binding osteoblasts to extracellular matrix o M-CSF  Macrophage colony stimulating factor  Located on the surface of the bone  Organelles of osteoblasts are polarized  Extend processes to make contact with near osteoblasts  Extend long processes to make contact with processes of osteocytes o Form gap junctions  Separated from the calcified matrix by thin, noncalcified layer, osteoid  Bone-lining cells: surface osteoblasts that cease to form matrix o Incapable of dividing o Can be reactivated with proper stimulus  Osteoblasts have several factor on their cell membranes o Integrins

o Parathyroid hormone receptors  Bind parathyroid hormone  Stimulate osteoblasts to secrete o Osteoprotegerin ligand (OPGL)  Induces the differentiation of preosteoclasts into osteoclasts  Increases RANKL expression o Osteoclast-stimulating factor  Activates osteoclasts to resorb bone o Enzymes responsible for removing osteoid  Osteoblasts can make contact with the mineralized bone surface.

Osteocytes Osteocytes are mature bone cells derived from osteoblasts that became trapped in their lacunae.  Derived from osteoblasts  Housed in lacunae within calcified bony matrix  Canaliculi: tunnel like spaces radiating out in all directions from the lacuna o House the cytoplasmic process of osteocyte o Make contact with similar processes of neighboring osteocytes  Form gap junctions o Contain extracellular fluid  Concerned in mechanotransduction o Respond to stimuli that place tension on bone by releasing  Cyclic adenosine monophosphate (cAMP)  Osteocalcin  Insulin-like growth factor o Facilitate recruitment of preosteoclasts for remodeling of the skeleton (add more bone)  Periosteocytic space: interval between the osteocyte plasmalemma and the walls of the lacunae and canaliculi o Occupied by extracellular fluid (1,3 L)

Osteoclasts Osteoclasts are multinucleated cells originating from granulocyte-macrophage progenitors. They play a role in bone resorption.  Precursors in bone marrow  Have receptors for o Osteoclast-stimulating factor o Colony-stimulating factor-1 o Osteoprotegerin (OPG) o Calcitonin  Responsible for resorbing bone and then they undergo apoptosis Morphology of osteoclasts  Have up to 50 nuclei  Have precursor in common with monocytes (mononuclear phagocyte system) o Stimulated by macrophage colony-stimulating factor to undergo mitosis  Osteoblasts secrete 3 signaling molecules that regulate the differentiation of osteoclasts o Macrophage colony-stimulating factor (M-CSF)  Bind to a receptor on the osteoclast precursor  Induces the activation of nuclear factor kappa B (RANK) o RANKL  Bind to RANKL receptor on osteoclastic precursor  Inducing it to differentiate into osteoclast, activate it and enhance bone resorption o OPG

Member of tumor necrosis factor receptor (TNFR) family Interact with RANKL, prohibit it from binding to macrophage, and inhibit osteoclast formation. Tensional forces on bone trigger OPG and mRNA synthesis Osteoclast occupy shallow depressions, Howship’s lacunae Osteoclast active in bone resorption may subdivided into 4 regions o Basal zone  Located farthest from Howship’s lacunae  Houses most of the organelles o Ruffled border  Directly involved in resorption of bone  Has finger-like processes projecting into resorption compartment, subosteoclastic compartment.  Has a coat on the cytoplasmic aspect  Mitochondria more numerous near ruffled border o Clear zone  Immediately surround the periphery of the ruffled border  Organelle-free  Contain actin microfilament that form an actin ring  Must be formed for bone resorption  Its formation is facilitated by OPGL  Ruffled border formed then  Its plasma membrane is so closely applied to the bone  Form sealing zone of the subosteoclastic compartment o Vesicular zone  Consist of endocytotic and exocytotic vesicles  Ferry lysosomal enzymes and metalloproteinases into the subosteoclastic compartment  Ferry products of degradation into the cell  Located between basal zone and ruffled border  

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Mechanism of bone resorption  Carbonic acid (H2CO3) formed from carbon dioxide and water o Catalyzed by carbonic anhydrase o Dissociates into  H+ ions  Bicarbonate ions HCO3 Accompany Na+ and cross the plasma lemma and enter nearby capillaries  Plasmalemma of ruffled border actively transport H+ ions into the subosteoclastic compartment o Reduce pH  Inorganic component is dissolved due to acidic environment  Liberated minerals enter osteoclast cytoplasm to be delivered to nearby capillaries  Lysosomal hydrolases + metalloproteinases o Collagenase + gelatinase  Secreted by osteoclasts into subosteoclastic compartment  Degrade the organic components of the decalcified bone matrix  Products are endocytosed by osteoclasts, further broken and released into capillaries Hormonal control of bone resorption  Parathyroid hormone o Produced by parathyroid gland  Calcitonin o Produced by thyroid gland

Bone structure Bones are classified according to their anatomical shape: long, short, flat, irregular and sesamoid.  Long bones o Has a shaft located between 2 heads o Tibia  Short bones o Have the same length and width o Carpal bones of the wrist  Flat bones o Flat, thin, plate-like o Bones of the skull  Irregular bones o Sphenoid and ethmoid bones  Sesamoid bones o Develop within tendons o Patella

Gross observation of bone 

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Compact bone: the very dense bone on the outside surface o Contain trabeculae and spicules jutting out from the internal surface into the marrow cavity Cancellous or spongy bone: porous portion lining the marrow cavity o Lack haversian systems o Has lamellae  Contain lacunae housing osteocytes Bone marrow o Red bone marrow  Contain forming blood cells o Yellow bone marrow  Composed of fat Diaphysis: shaft of long bone o Covered with periosteum  Except where tendons and muscles insert into the bone  Not on surfaces covered by articular cartilage  Absent on sesamoid bones (patella)  Inserted into the bone by Sharpey’s fibers Epiphysis: articulating end of long bone o Covered with a thin layer of compact bone o Covered with hyaline cartilage Epiphyseal plate: cartilage separating diaphysis from epiphysis in growing persons Metaphysis: the area between epiphyseal plate and diaphysis Flat bones (skull cap) o Compact bone  Inner table  Lined with dura mater internally  Outer table  Has periosteum known as pericranium o Spongy bone  Diploë

Bone types based on microscopic observations Microscopically, bone is classified as either primary (immature) or secondary (mature) bone  Primary bone, immature bone, woven bone o The first bone to form during fetal development and during bone repair o Has abundance of osteocytes and irregular bundles of collagen  Replaced and organized as secondary bone except at  Sutures of the calvaria  Insertion sites of tendons  Bony alveoli surrounding the teeth o Has less minerals  Secondary bone, mature bone, lamellar bone o Composed of lamellae

Lamellar system of compact bone There are four lamellar systems in compact bone: outer circumferential lamellae, inner circumferential lamellae, osteons and interstitial lamellae.  Outer circumferential lamellae o Deep to the periosteum o Form the outermost region of the diaphysis o Contain Sharpey’s fibers anchoring the periosteum to the bone  Inner circumferential lamellae o Encircle the marrow cavity o Trabeculae from spongy bone extend from inner circumferential lamellae into the marrow cavity  Haversian canal systems (osteons) o Composed of cylinders of lamella  Surround a vascular space known as haversian canal o Bifurcate along their length o Each osteon is bounded by cementing line  Composed of calcified ground substance with collagen fibers o Lined by a layer of osteoblasts and osteoprogenitor cells o Haversian canals of adjacent osteons are connected by Volkmann’s canals  Interstitial lamellae o Remnants of osteons o Surrounded by cementing lines

Histogenesis of bone Intramembranous bone formation Intramembranous bone formation occurs within mesenchymal tissue.  Most flat bones are formed by intramembranous bone formation.  Primary ossification center o Region where mesenchymal cells differentiate into osteoblasts  Secrete bone matrix forming a network of spicules and trabeculae  Their collagen are randomly oriented  Calcification follows osteoid formation  Osteoblasts becomes trapped and known as osteocytes o Their processes are also surrounded by bone and form canaliculi o Mesenchymal cells differentiate into osteoprogenitor cells which differentiate into osteoblast and the process of bone formation continues  Vascular connective tissue in the trabeculae become transformed into bone marrow  Fontanelles represents ossification centers that are not f...