Histology Ch 7 198-209
Cartilage
-Cartilage is avascular CT composed of chondrocytes with highly specialized extracellular matrix
-Extracellular matrix in cartilage is solid and firm but pliable which accounts for resilience
-Large ratio of glycosaminoglycans to type II collagen fibers permits diffusion between vessels
-Types of cartilage are:
1. Hyaline Cartilage – type II collagen, GAGs, proteoglycans, and glycoproteins
2. Elastic Cartilage – elastic fibers and lamellae in addition to matrix of hyaline cartilage
3. Fibrocartilage – type I collagen w/ matrix of hyaline cartilage
Hyaline Cartilage – hyaline cartilage is distinguished by a homogenous, amorphous matrix,
which has spaces called lacunae spaced out throughout cartilage matrix w/ chondrocytes
-shows no evidence of abrasive wear over a lifetime, except in articular cartilage which breaks
down with age
-Hyaline matrix is produced by chondrocytes and contains 3 classes of molecules:
1. Collagen – 4 types of collagen participate in matrix fibrils. Type II collagen has the
bulk, type IX collagen facilitates fibril interaction with matrix proteoglycans; type XI
collagen regulates fibril size; and type X collagen – organizes collagen fibrils into 3D
lattice. Type VI collagen is found at periphery where it helps attach cells to framework
-Types II, VI, IX, X, XI are called cartilage-specific collagen molecules
2. Proteoglycans – ground substance of cartilage contains 3 types of GAGS: hyaluronan,
chondroitin sulfate, and keratan sulfate
-chondroitin and keratin sulfate joined to form proteoglycan, most important of
which is called aggrecan
-hyaluronan is associated with aggrecan to form proteoglycan aggregates
bound to collagen matrix fibrils responsible for biomechanical properties of
hyaline cartilage
3. Multiadhesive Glycoproteins – noncollagenous and nonproteoglycan-linked
glycoproteins influence interactions between chondrocytes and matrix
-clinical markers of cartilage turnover and degeneration, such as protein
anchorin CII (annexin V), Tenascin, and fibronectin which help chondrocytes
anchor to matrix
-hyaline cartilage is hydrated to provide resilience and diffusion of small metabolites (70% H2O)
-water is bound tightly to aggregan-hyaluronan aggregates, but allows diffusion of
molecules
-chondrocytes are special cells that produce and maintain extracellular matrix
-in hyaline cartilage, chondrocytes are distributed singly or in clusters called isogenous groups,
which represent cells that have recently divided
-new cells secrete matrix and metalloproteinases, enzymes that degrade cartilage so that they
can expand and reposition themselves
Matrix does not stain homogenously and is therefore divided into regions
1. Capsular (pericellular) matrix – ring of dense matrix directly around chondrocyte with
the highest concentration of type VI collagen to anchor cell with integrins onto matrix
2. Territorial Matrix – region more removed from vicinity of cell, and has type II collagen
with small type IX collagen
3. Interterritorial Matrix – surround territorial matrix and is space around isogenous group
-hyaline cartilage provides a model for the developing skeleton of the fetus
-In fetal development, hyaline cartilage is precursor for endochondral ossification, where long
bones were once cartilage models that resemble the shape of mature bone
-cartilage is replaced by bone, and the remaining cartilage remains in a site called the
epiphyseal growth plate to keep the bones growing
-perichondrium is a firmly attached dense CT that surrounds hyaline cartilage and serves as a
source of new cartilage cells
-hyaline cartilage of articular joint surfaces does NOT possess a perichondrium, and articular
cartilage is divided into 4 zones:
1. Superficial (tangential) zone – pressure resistant region close to articular surface formed
from elongated and flattened chondrocytes surrounded by a calcified line called a tidemark
-above this line, proliferation of chondrocytes within cartilage lacunae provides new
cells for interstitial growth
Clinical Correlation (Osteoarthritis) – degenerative joint disease related to aging and articular
joint injury; characterized by chronic joint pain on weight-bearing joints
-decrease in proteoglycan content results in reduction of intercellular water content in matrix
-chondrocytes produce IL-1 and TNF-a to stimulate metalloproteinases and inhibit type II
collagen to disrupt articular cartilage, which later extends to bone
Elastic Cartilage – distinguished by presence of elastin in cartilage matrix which is a dense
network of branching and anastomosing elastic fibers and interconnecting sheets of elastic
material. It is resilient and pliable
-found in external ear, walls of external acoustic meatus, Eustachian tube, and epiglottis
-elastic cartilage does not calcify with aging
Fibrocartilage – consists of chondrocytes and their matrix material in combination with dense
connective tissue, where the cells are dispersed among collagen fibers singularly, in rows, and in
isogenous groups and have less cartilage matrix material than hyaline cartilage without a
surrounding perichondrium as in hyaline and elastic cartilages
-seen in intervertebral discs, pubic symphysis, articular discs of sternoclavicular and
temporomandibular joints, menisci of knee, and triangular fibrocartilage of wrist
-provides resistance to compression and shearing
-ECM of fibrocartilage is characterized by Type I and Type II collagen fibrils
-cells here synthesize ECM during development AND during mature stages to respond to
changes in external environment, requiring BOTH types of collagen
-ECM of fibrocartilage contains larger amounts of versican (proteoglycan secreted by
fibroblasts) that can bind to hyaluronan to form highly hydrated proteoglycan aggregates
Chondrogenesis and Cartilage Growth – most cartilage arises from mesenchyme during
chondrogenesis, and begins with aggregation of chondroprogenitor mesenchymal cells forming
a mass of round cells
-in hyaline cartilage, an aggregation of mesenchymal or ectomesenchymal cells known as a
chondrogenic nodule express SOX-9 to differentiate these cells into chondroblasts which
secrete cartilage matrix (type II collagen) until completely surrounded, then they are called
chondrocytes. It is regulated by many extracellular ligands, transcription factors, adhesion
molecules, and matrix proteins
Cartilage is capable of appositional and interstitial growth:
1. Apposition growth – process forming new cartilage at surface of existing cartilage
a. New cartilage produced is from inner portion of surrounding perichondrium,
cells resemble fibroblasts and produce type I collagen, and then differentiate
upon expression of SOX-9 and secrete type II collagen
2. Interstitial growth – forms new cartilage within existing cartilage mass, from division of
existing chondrocytes within their lacunae, and the daughter cells occupy the same
lacuna
Repair of Hyaline Cartilage – cartilage has LIMITED ability for repair, attributable to the lack of
vascularity of cartilage, immobility of chondrocytes, and limited ability of chondrocytes to
proliferate
-some repair can occur if defect occurs at perichondrium
-repair consists of balance between deposition of type I collagen in form of scar tissue and
repair by expression of cartilage-specific collagens
-new blood vessels in adults commonly develop at site of healing wound to stimulate bone
growth rather than actual cartilage repair
When hyaline cartilage calcifies, it is replaced by bone, a process in which calcium phosphate
crystals are embedded in the cartilage matrix in 3 situations
1. portion of articular cartilage is in contact with bone tissue is calcified
2. calcification always occurs in cartilage that is about to be replaced by bone during an
individual’s growth period
3. hyaline cartilage in adult calcifies with time as part of agine process
-some people believe process of cartilage removal involves a cell called a chondroclast, which
resembles an osteoclast
Clinical Correlation: Malignant Tumors of Cartilage – Chondrosarcomas – slow growing
malignant tumors characterized by secretion of cartilage matrix; occur predominantly in axial
skeleton in vertebrae, pelvic bones, ribs, scapulae, and sternum, and at metaphyses of proximal
ends of long bones in femur and humerus
-Presence of collagen types II and X in biopsies are associated with good prognosis