specialised connective tissue and ECM: cartilage Flashcards
lecture 11
What is the cellular content of connective tissues compared to other tissues?
Connective tissues have reduced cellular content and rare cell-cell contact compared to epithelial, muscle, and nervous tissues.
What is the main stress-bearing component of connective tissues?
The extracellular matrix (ECM) is the main stress-bearing component.
What does the ECM provide in terms of cell interaction?
The ECM forms an indirect means of cell-cell contact.
What are the main components of the ECM?
The ECM consists of fibrous proteins and hydrated proteoglycans surrounding cells in tissues.
List four functions of the ECM.
Strengthens and supports tissues.
Guides cell migration and polarity.
Transports nutrients and waste.
Permits intercellular communication.
What ensures the maintenance of a healthy ECM?
A balance between synthesis and breakdown of ECM components ensures its maintenance.
What are the three main types of cartilage?
Hyaline, fibrocartilage, and elastic cartilage.
Where is hyaline cartilage found, and what are its key features?
Hyaline cartilage is found in ribs, nose, larynx, trachea, and articular joints. It acts as a precursor for bone and is characterised by indigenous chondrocytes.
Where is fibrocartilage located, and what are its properties?
Fibrocartilage is found in joint capsules and ligaments. It is the least flexible type of cartilage with the highest collagen content and fewest cells.
Where is elastic cartilage found, and why is it highly flexible?
Elastic cartilage is found in the ear, epiglottis, and larynx. Its flexibility is due to increased elastin content.
What are the two key components of articular cartilage?
Type II collagen and aggrecan.
What happens when the integrity of collagen in the ECM is compromised?
Loss of collagen integrity leads to a reduction in the strength of the ECM.
What genetic disorder is associated with defective collagen deposition?
Ehlers-Danlos syndrome, which results in hyperextensible joints.
What condition is caused by a mutation in the COL18A1 gene?
Knobloch syndrome.
Why are proteoglycans (PG) in cartilage highly charged?
They contain glycosaminoglycans (GAGs), which attract water to form a hydrated gel.
What are the three functions of the hydrated gel formed by proteoglycans?
Provides resistance to compression.
Generates swelling pressure (turgor).
Adds strength and support to the tissue.
What is the only cell type found in adult cartilage?
Chondrocytes.
What is the typical structure and grouping of chondrocytes?
Chondrocytes are large, mature cells that are grouped in clusters of 2-8 cells.
What organelles are abundant in chondrocytes, and why?
Chondrocytes are rich in RER and Golgi apparatus, facilitating the secretion of type II collagen and aggrecan.
What are three defining characteristics of the ECM where chondrocytes reside?
The ECM is avascular, alymphatic, and aneuronal.
From which precursor do chondrocytes differentiate?
Mesenchymal stem cells (MSCs).
What transcription factor is key to chondrocyte differentiation?
Sox-9, which induces Col2A expression.
Name three growth factors that drive chondrocyte proliferation and ECM synthesis.
TGF-β, fibroblast growth factor (FGF), and insulin-like growth factor (IGF-1).
What type of ossification involves the replacement of cartilage by bone?
Endochondral ossification.
Where does endochondral ossification occur, and what does it involve?
It occurs in long bones and involves the replacement of a cartilage model by bone tissue.
How are morphogens involved in cartilage spatial patterning?
Morphogens, like Hedgehog proteins, regulate chondrocyte spatial arrangement through inductive signalling.
Name three types of Hedgehog proteins involved in chondrocyte signalling.
Sonic Hedgehog (SHH), Desert Hedgehog (DHH), and Indian Hedgehog (IHH).
What is the role of IHH and PTHrP in cartilage development?
They maintain chondrocyte proliferation and prevent terminal differentiation through positive feedback loops.
What happens to chondrocytes as they move farther from PTHrP sources?
They differentiate into osteoblast-like cells and contribute to ossification.
What are the main features of articular cartilage?
Connective tissue ECM directs bone development during embryogenesis.
Permits mechanical load and movement of articulated bones.
Contains a single cell type: chondrocytes.
What structural ECM component in bone provides its rigidity?
Hydroxyapatite, found in the osteoid ECM.
How do mesenchymal stem cells contribute to skeletal tissue formation?
They differentiate into various cell types, including chondrocytes, osteoblasts, and adipocytes, depending on signalling cues.
How do proteoglycans contribute to cartilage resilience?
By attracting water, they form a gel that resists compression and enhances tissue durability.
Why is the cartilage ECM hypoxic?
It is avascular, meaning it lacks a direct blood supply.
Why is the ECM critical for intercellular communication in tissues?
The ECM acts as a medium through which signalling molecules can pass, enabling communication between distant cells.
What happens to chondrocytes during embryonic development?
They differentiate from mesenchymal stem cells and secrete components like type II collagen and aggrecan to establish the cartilage ECM.
What process ensures the balance between cartilage production and degradation in the ECM?
The balance is regulated by enzymes and signalling pathways involved in ECM synthesis and breakdown.
What are lacunae, and how do they form during ossification?
Lacunae are cavities that form when chondrocytes die and leave spaces in the cartilage matrix during endochondral ossification.
What are the main signalling pathways involved in cartilage and bone formation?
Hedgehog signalling and PTHrP-mediated pathways play critical roles in regulating chondrocyte proliferation and differentiation.
How does Sox-9 influence the development of cartilage?
Sox-9 activates the expression of collagen type II (Col2A) and promotes chondrocyte differentiation and ECM production.
What is the role of TGF-β in cartilage development?
TGF-β supports chondrocyte proliferation and stimulates ECM synthesis, contributing to cartilage formation.
What is the function of osteoblasts in endochondral ossification?
Osteoblasts replace cartilage with bone matrix, contributing to the formation of long bones.
How does the ECM influence cell polarity and migration?
The ECM provides physical and chemical cues that guide the orientation (polarity) and movement (migration) of cells.
What is the role of IHH in long bone formation?
Indian Hedgehog (IHH) regulates PTHrP production, ensuring proper spatial organisation and timing of chondrocyte differentiation.
How does Hedgehog signalling regulate gene expression in cartilage development?
Hedgehog proteins inhibit the repressor proteins, allowing the activation of genes essential for chondrocyte function and proliferation.
What are morphogens, and why are they important in skeletal development?
Morphogens are signalling molecules that control tissue patterning by guiding the spatial arrangement of chondrocytes and other cells.
How does fibrocartilage provide support in areas of high stress?
Its high collagen content and low cell density make it the strongest and least flexible type of cartilage, ideal for load-bearing structures.
Why is elastic cartilage more flexible than other types of cartilage?
Elastic cartilage contains a higher concentration of elastin, allowing it to return to its shape after deformation.
What happens during cartilage catabolism in ossification?
Cartilage is broken down and replaced with calcified bone matrix during the ossification process.
What is the composition of the osteoid ECM in bone?
It contains hydroxyapatite (a mineral) and collagen, providing rigidity and tensile strength.
How does the avascular nature of cartilage affect its healing?
The lack of blood vessels limits the delivery of nutrients and repair cells, making cartilage slow to heal.
What causes hypoxic conditions in cartilage?
The absence of blood vessels (avascularity) creates low oxygen conditions, which chondrocytes adapt to by relying on anaerobic metabolism.
Why is chondrocyte metabolism adapted to hypoxic environments?
Chondrocytes rely on anaerobic pathways because the avascular cartilage ECM cannot deliver sufficient oxygen.
What is the significance of the cartilage model in fetal development?
The cartilage model serves as a template for bone formation during endochondral ossification.
How does PTHrP prevent premature differentiation of chondrocytes?
PTHrP maintains chondrocytes in a proliferative state, delaying their terminal differentiation into osteoblast-like cells.
What is the role of glycosaminoglycans (GAGs) in the ECM?
GAGs attract water, forming a gel-like structure that provides resistance to compressive forces.
What is the relationship between IHH and PTHrP in bone development?
IHH stimulates PTHrP production, creating a feedback loop that maintains cartilage production and chondrocyte proliferation.
How does collagen biosynthesis affect cartilage integrity?
Proper collagen biosynthesis is essential for maintaining the tensile strength of the cartilage matrix.
What is the function of chondrocyte-secreted type II collagen in cartilage?
Type II collagen provides structural support and tensile strength to the ECM.
How do proteoglycans contribute to the biomechanical properties of cartilage?
By forming a hydrated gel, proteoglycans resist compressive forces and maintain tissue elasticity.
