Cartilage

chondrocyte development

-chondroblasts become chondrocytes once they are completely surrounded by matrix material

aggrecan

-Aggrecan is the most important proteoglycan monomer in hyaline cartilage -Due to the presence of the sulfate groups, aggrecan molecules have a large negative charge with an affinity for water molecules. -A hyaluronan molecule is associated with a large number of aggrecan molecules (> 300), bound to the hyaluronan by link proteins at the N terminus of the molecule to form large proteoglycan aggregates -Highly charged proteoglycan aggregates are bound to collagen matrix fibrils by electrostatic interactions and multiadhesive glycoproteins -Entrapment of proteoglycan aggregates w/in the matrix of collagen fibrils is responsible for the biomechanical properties of hyaline cartilage.

Repair of cartilage

-Cartilage has limited ability for repair -Cartilage can tolerate considerable intense and repetitive stress -When damaged cartilage has a striking inability to heal, even in the most minor injuries -Lack of response to injury is attributable to the avascularity of cartilage, the immobility of chondrocytes and the limited ability of mature chondrocytes to proliferate -Some repair can occur but only if the defect involves the perichondrium -Repair in these injuries results from pluripotential progenitor cells in the perichondrium -Even then, few cartilage cells, if any are produced -Repair mostly involves production of dense CT -Molecularly: collagen repair is a tentative balance b/t deposition of type I collagen in the form of scar tissue and repair by expression of the cartilage-specific collagens -In adults new blood vessels commonly develop at the site of the healing wound that stimulate bone growth rather than actual cartilage repair -Certain tx may improve healing of articular cartilage: perichondrial grafts, autologous cell transplantation, insertion of artificial matrices and application of growth factors

collagen molecules in the HYALINE cartilage matrix

-Collagen is the major matrix protein. -Type II collagen constitutes the bulk of the fibrils -Type IX collagen facilitates fibril interaction with the matrix proteoglycan molecules -Type XI collagen regulates the fibril size -Type X collagen organizes the collagen fibrils into a 3D hexagonal lattice (crucial to mechanical fxn) -Type VI collagen is also found in the matrix, mainly at the periphery of the chondrocytes where it helps to attach these cells to the matrix framework (not a main collagen of hyaline cartilage) -Types II, VI, IX, X, and XI only found significantly in the cartilage matrix (referred to as cartilage-specific collagen molecules)

Hyaline cartilage role in fetal bone development

-Hyaline cartilage is the precursor to bone in early fetal development -Develop through endochondral ossification -During development most cartilage is replaced by bone, residual cartilage at the proximal and distal ends of the bone serve as growth sites (epiphyseal growth plates) -The cartilage in this area remains functional as long the bone grows in length -When growth is complete the remnant of cartilage is found on the articular surface of joints (articular cartilage) and in the rib cage (costal cartilage) -Hyaline cartilage also exists in the adult as the skeletal unit in the trachea, bronchi, larynx and nose

hydration of hyaline cartilage

-Hyaline cartilage matrix is highly hydrated to provide resilience and diffusion of small metabolites -A lot of the water in hyaline cartilage is tightly bound to aggrecan-hyaluronan aggregates, creating high osmotic swelling pressure -some H2O is bound loosely enough to allow diffusion of small metabolites to and from the chondrocytes -The high degree of hydration and movement of water in the matrix allow the cartilage matrix to respond to varying pressure loads and contribute to cartilage's weight-bearing capacity

what macromolecules make up the hyaline cartilage matrix?

-Hyaline cartilage matrix is produced by chondrocytes and contains collagen molecules, proteoglycans and multiadhesive glycoproteins

multiadhesive glycoproteins associated with HYALINE cartilage

-Multiadhesive glycoproteins (noncollagenous and nonproteoglycan-linked glycoproteins) -influence interactions b/t the chondrocytes and the matrix molecules. -Clinically significant markers of cartilage turnover and degeneration

proteoglycans associated w/HYALINE cartilage

-The ground substance of hyaline cartilage contains three kinds of glycosaminoglycans: hyaluronan, chondroitin sulfate, and keratan sulfate. -Chondroitin and keratan sulfate of the cartilage matrix are joined to a core protein to form a proteoglycan monomer (similar to loose CT matrix) -Aggrecan is the most important proteoglycan monomer in hyaline cartilage -Cartilage matrix also contains other proteoglycans that do not form aggregates but bind to other molecules and help stabilize the matrix.

situations in which the matrix of hyaline cartilage undergoes calcification

-The matrix of hyaline cartilage undergoes calcification as a regular occurrence in three situations: 1. The portion of articular cartilage that is in contact with bone tissue in growing and adult bones, but not the surface portion, is calcified. 2. Calcification always occurs in cartilage that is about to be replaced by bone (endochondral ossification) during an individual's growth period. 3. Hyaline cartilage in the adult calcifies with time as part of the aging process. -In most of these situations, given sufficient time, cartilage that calcifies is replaced by bone.

perichondrium development

-The mesenchymal tissue immediately surrounding the chondrogenic nodule gives rise to the perichondrium

renewal of mature articular cartilage

-The renewal process of mature articular cartilage is very slow -slow growth is a reflection of the highly stable type II collagen network and the long half-life of its proteoglycan molecules -in healthy articular cartilage, metalloproteinase (MMP-1 and MMP-13) activity is low

cartilage-specific collagen molecules

-Types II, VI, IX, X, and XI only found significantly in the cartilage matrix (referred to as cartilage-specific collagen molecules)

calcification of hyaline cartilage

-When hyaline cartilage calcifies, it is replaced by bone. -Hyaline cartilage is prone to calcification -calcium phosphate crystals become embedded in the cartilage matrix. -Chondrocytes normally derive all of their nutrients and dispose of wastes by diffusion of materials through the matrix. -When the matrix becomes heavily calcified, diffusion is impeded and the chondrocytes swell and die -Leads to the removal of the calcified matrix and its replacement by bone

territorial matrix

-a region that surrounds the isogenous group and contains a randomly arranged network of type II collagen fibrils with smaller quantities of type IX collagen -lower concentration of sulfated proteoglycans and stains less intensely than the capsular matrix.

appositional growth of cartilage

-appositional growth: the process that forms new cartilage at the surface of an existing cartilage -New cartilage cells produced during appositional growth are derived from the inner portion of the surrounding perichondrium -The cells resemble fibroblasts in form and function, producing the collagen component of the perichondrium (type I collagen) -When cartilage growth is initiated the cells undergo differentiation guided by SOX-9 expression -The cytoplasmic processes disappear, the nucleus becomes rounded and the cytoplasm increases in amt. And prominence -These changes lead to the cell becoming a chondroblast -Chondroblasts fxn in cartilage matrix production (including type II collagen secretion) -New matrix increases cartilage mass, while new fibroblasts are produced simultaneously to maintain the cell population of the perichondrium

Chondroclasts

-believed to be involved in cartilage removal -resemble osteoclasts in morphology and fxn -identified in calcified and non-calcified articular erosions in RA -express osteoclast type phenotype -It is likely that chondroclasts are mature osteoclasts capable of resorbing cartilage and are found where cartilage is being removed

chondrocyte isogenous groups

-called isogenous groups -Chondrocytes in isogenous groups represent cells that have recently divided -As chondrocytes produce the matrix material that surrounds them, they become dispersed. -They also secrete metalloproteinases (degrade cartilage matrix) allowing the cells to expand and reposition themselves within the growing isogenous group.

internal remodeling

-cartilage undergoes continuous internal remodeling s the cells replace matrix molecules lost through degradation -normal turnover depends on the ability of chondrocytes to detect changes in matrix composition -chondrocytes respond by synthesizing appropriate types of new molecules -the matrix acts as a signal transducer for the embedded chondrocytes

calcified zone

-characterized by a calcified matrix with the presence of small chondrocytes -separated from the deep (radial) zone by a smooth, undulating, heavily calcified line called the tidemark -Above the tidemark proliferation of chondrocytes within the cartilage lacunae provides the new cells for interstitial growth. -In articular cartilage renewal, chondrocytes migrate from this region toward the joint surface.

fibrocartilage

-characterized by abundant type I collagen fibers as well as the matrix material of hyaline cartilage -Fibrocartilage is a combination of dense regular CT and hyaline cartilage -The chondrocytes are dispersed among the collagen fibers singularly, in rows and in isogenous groups -The chondrocytes appear similar to the chondrocytes of hyaline cartilage but have considerably less cartilage matrix material -NO SURROUNDING PERICHONDRIUM -typically present in IV discs, pubic symphysis, articular discs of sternoclavicular and temporomandibular joints, menisci, triangular fibrocartilage complex of the wrist and certain places where tendons attach to bones -presence of fibrocartilage indicates resistance to compression and shearing forces required of the tissue

elastic cartilage

-characterized by elastic fibers and elastic lamellae in addition to the matrix material of hyaline cartilage -elastic material gives the cartilage elastic properties in addition to the resilience and pliability that are characteristic of hyaline cartilage -found in the external ear, the walls of the external acoustic meatus, the auditory (Eustachian) tube, and the epiglottis of the larynx -surrounded by perichondrium (like hyaline cartilage) -unlike hyaline cartilage the matrix does not calcify during the aging process

hyaline cartilage

-characterized by matrix containing type II collagen fibers, GAGs, proteoglycans and multiadhesive glycoproteins -Distinguished by homogeneous amorphous matrix -The matrix of hyaline cartilage appears glassy in the living state -Throughout the cartilage matrix are spaces called lacunae. -Chondrocytes are located w/in the lacunae -Hyaline cartilage provides a low-friction surface, participates in lubricating synovial joints, and distributes applied forces to the underlying bone. -Limited capacity for repair (but shows no evidence of abrasive wear over a lifetime except articular cartilage (breaks down w/age))

deep (radial) zone

-characterized by small, round chondrocytes that are arranged in short columns perpendicular to the free surface of the cartilage -collagen fibrils are positioned between columns parallel to the long axis of the bone.

ECM of fibrocartilage is characterized

-characterized by the presence of type I and type II collagen fibrils -Cells in fibrocartilage synthesize a wide variety of ECM molecules during both developmental and mature, fully differentiated states -Relative proportions of type I and type II collagen in fibrocartilage varies -Ratio of type 1: type II collagen in fibrocartilage changes w/age -More type II collagen in older individuals -ECM of fibrocartilage contains larger amounts of versican (a proteoglycan monomer secreted by fibroblasts) -Can bind hyaluronan to form highly hydrated proteoglycan aggregates -IV disc degeneration is associated w/proteolytic degradation of proteoglycan aggregates present w/in the ECM of the fibrocartilage

chondrocyte appearance in cytoplasm

-chondrocyte appearance in cytoplasm varies according to chondrocyte activity -chondrocytes that are active in matrix production display areas of cytoplasmic basophilia (indicates proteins synthesis), and clear areas (location of Golgi) -Golgi is smaller in older less active cells (the clear space indicates sites of extracted lipid droplets and glycogen stores)

chondroblasts

-differentiated by expression of SOX9 from chondrogenic nodules -expression of SOX-9 is associated w/secretion of type II collagen -chondroblasts progressively move apart as they deposit matrix

chondrogenic nodule

-during development -The site of hyaline cartilage formation is recognized initially by an aggregate of mesenchymal or ectomesenchymal cells known as chondrogenic nodule

ECM in cartilage

-firm but pliable (accounts for resilience) -no vascular network -large ration of GAGs to type II collagen fibers (permits diffusion of substances b/t blood vessels in the surrounding CT and the chondrocytes dispersed w/in the matrix, maintaining viability of tissue) -close interactions occur b/t the tension-resisting collagen fibrils and the large amts. of heavily hydrated proteoglycan aggregates

capsular (pericellular) matrix

-hyaline cartilage -ring of more densely staining matrix located immediately around the chondrocyte -contains the highest concentration of sulfated proteoglycans, hyaluronan, biglycans, and several multiadhesive glycoproteins -contains almost exclusively type VI collagen fibrils (forms a tightly woven enclosure around each chondrocyte) -Type VI collagen binds to integrin receptors on the cell surface and anchors the chondrocytes to the matrix -A higher concentration of type IX collagen is also present in the capsular matrix.

superficial (tangential) zone

-is a pressure-resistant region closest to the articular surface -contains numerous elongated and flattened chondrocytes surrounded by a condensation of type II collagen fibrils that are arranged in fascicles parallel to the free surface

intermediate (transitional) zone

-lies below the superficial zone and contains round chondrocytes randomly distributed within the matrix. -Collagen fibrils are less organized and are arranged in a somewhat oblique orientation to the surface

Chondrogenesis and cartilage growth

-most cartilage arises from mesenchyme during chondrogenesis -chondrogenesis begin w/the aggregation of chondroprogenitor mesenchymal cells to form a mass of rounded closely apposed cells -In the head most cartilage arises from aggregates of ectomesenchyme derived from neural crest cells -the site of hyaline cartilage formation is recognized as an aggregate of mesenchymal or ectomesenchymal cells known as chondrogenic nodule -Expression of transcription factor SOX-9 triggers differentiation of these cells into chondroblasts, which secrete cartilage matrix -Expression of SOX-9 is associated w/secretion of type II collagen -Chondroblasts progressively move apart as they deposit matrix -The cells are called chondrocytes when they are completely surrounded by matrix material

perichondrium

-surrounds hyaline and elastic cartilage BUT NOT fibrocartilage -It is a dense irregular CT composed of cells that are indistinguishable from fibroblasts -Serves as the source of new cartilage cells -The perichondrium appears divided into an inner cellular layer (gives rise to new cartilage cells), and an outer fibrous layer when it is actively growing -The division of these layers is not always evident (especially in new, or slow-growing cartilage) -Hyaline cartilage of articular joint surfaces does not possess a perichondrium -Articular cartilage is a remnant of developing bone and persists through adult life

interstitial growth

-the process that forms new cartilage within an existing cartilage mass. -New cartilage cells produced during interstitial growth arise from the division of chondrocytes w/in their lacunae -Chondrocytes retain the ability to divide and the surrounding matrix is distensible, permitting further secretory activity -Initially the daughter cells of dividing chondrocytes occupy the same lacuna -As new matrix is secreted, a partition is formed b/t the daughter cells so each cell occupies its own lacuna -w/continued secretion of matrix the cells move further from one another -Overall growth of cartilage results from the interstitial secretion of matrix material by chondrocytes and by the appositional secretion of matrix material by newly differentiated chondroblasts

4 zones of articular cartilage

1. superficial (tangential) zone 2. intermediate (transitional) zone 3. deep (radial) zone 4. calcified zone

interterritorial matrix

is a region that surrounds the territorial matrix and occupies the space between groups of chondrocytes

chondrocytes

specialized cells that produce and maintain the ECM -secrete collagen present in the matrix as well as glycosaminoglycans and proteoglycans -either singularly distributed or in clusters called isogenous groups