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BMS2002: Cell Biology and Disease immunology > specialised connective tissue and ECM: cartilage > Flashcards

specialised connective tissue and ECM: cartilage Flashcards

lecture 11

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1
Q

What is the cellular content of connective tissues compared to other tissues?

A

Connective tissues have reduced cellular content and rare cell-cell contact compared to epithelial, muscle, and nervous tissues.

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2
Q

What is the main stress-bearing component of connective tissues?

A

The extracellular matrix (ECM) is the main stress-bearing component.

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3
Q

What does the ECM provide in terms of cell interaction?

A

The ECM forms an indirect means of cell-cell contact.

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4
Q

What are the main components of the ECM?

A

The ECM consists of fibrous proteins and hydrated proteoglycans surrounding cells in tissues.

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5
Q

List four functions of the ECM.

A

Strengthens and supports tissues.
Guides cell migration and polarity.
Transports nutrients and waste.
Permits intercellular communication.

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6
Q

What ensures the maintenance of a healthy ECM?

A

A balance between synthesis and breakdown of ECM components ensures its maintenance.

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7
Q

What are the three main types of cartilage?

A

Hyaline, fibrocartilage, and elastic cartilage.

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8
Q

Where is hyaline cartilage found, and what are its key features?

A

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.

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9
Q

Where is fibrocartilage located, and what are its properties?

A

Fibrocartilage is found in joint capsules and ligaments. It is the least flexible type of cartilage with the highest collagen content and fewest cells.

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10
Q

Where is elastic cartilage found, and why is it highly flexible?

A

Elastic cartilage is found in the ear, epiglottis, and larynx. Its flexibility is due to increased elastin content.

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11
Q

What are the two key components of articular cartilage?

A

Type II collagen and aggrecan.

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12
Q

What happens when the integrity of collagen in the ECM is compromised?

A

Loss of collagen integrity leads to a reduction in the strength of the ECM.

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13
Q

What genetic disorder is associated with defective collagen deposition?

A

Ehlers-Danlos syndrome, which results in hyperextensible joints.

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14
Q

What condition is caused by a mutation in the COL18A1 gene?

A

Knobloch syndrome.

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15
Q

Why are proteoglycans (PG) in cartilage highly charged?

A

They contain glycosaminoglycans (GAGs), which attract water to form a hydrated gel.

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16
Q

What are the three functions of the hydrated gel formed by proteoglycans?

A

Provides resistance to compression.
Generates swelling pressure (turgor).
Adds strength and support to the tissue.

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17
Q

What is the only cell type found in adult cartilage?

A

Chondrocytes.

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18
Q

What is the typical structure and grouping of chondrocytes?

A

Chondrocytes are large, mature cells that are grouped in clusters of 2-8 cells.

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19
Q

What organelles are abundant in chondrocytes, and why?

A

Chondrocytes are rich in RER and Golgi apparatus, facilitating the secretion of type II collagen and aggrecan.

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20
Q

What are three defining characteristics of the ECM where chondrocytes reside?

A

The ECM is avascular, alymphatic, and aneuronal.

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21
Q

From which precursor do chondrocytes differentiate?

A

Mesenchymal stem cells (MSCs).

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22
Q

What transcription factor is key to chondrocyte differentiation?

A

Sox-9, which induces Col2A expression.

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23
Q

Name three growth factors that drive chondrocyte proliferation and ECM synthesis.

A

TGF-β, fibroblast growth factor (FGF), and insulin-like growth factor (IGF-1).

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24
Q

What type of ossification involves the replacement of cartilage by bone?

A

Endochondral ossification.

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25
Q

Where does endochondral ossification occur, and what does it involve?

A

It occurs in long bones and involves the replacement of a cartilage model by bone tissue.

26
Q

How are morphogens involved in cartilage spatial patterning?

A

Morphogens, like Hedgehog proteins, regulate chondrocyte spatial arrangement through inductive signalling.

27
Q

Name three types of Hedgehog proteins involved in chondrocyte signalling.

A

Sonic Hedgehog (SHH), Desert Hedgehog (DHH), and Indian Hedgehog (IHH).

28
Q

What is the role of IHH and PTHrP in cartilage development?

A

They maintain chondrocyte proliferation and prevent terminal differentiation through positive feedback loops.

29
Q

What happens to chondrocytes as they move farther from PTHrP sources?

A

They differentiate into osteoblast-like cells and contribute to ossification.

30
Q

What are the main features of articular cartilage?

A

Connective tissue ECM directs bone development during embryogenesis.
Permits mechanical load and movement of articulated bones.
Contains a single cell type: chondrocytes.

31
Q

What structural ECM component in bone provides its rigidity?

A

Hydroxyapatite, found in the osteoid ECM.

32
Q

How do mesenchymal stem cells contribute to skeletal tissue formation?

A

They differentiate into various cell types, including chondrocytes, osteoblasts, and adipocytes, depending on signalling cues.

33
Q

How do proteoglycans contribute to cartilage resilience?

A

By attracting water, they form a gel that resists compression and enhances tissue durability.

34
Q

Why is the cartilage ECM hypoxic?

A

It is avascular, meaning it lacks a direct blood supply.

35
Q

Why is the ECM critical for intercellular communication in tissues?

A

The ECM acts as a medium through which signalling molecules can pass, enabling communication between distant cells.

36
Q

What happens to chondrocytes during embryonic development?

A

They differentiate from mesenchymal stem cells and secrete components like type II collagen and aggrecan to establish the cartilage ECM.

37
Q

What process ensures the balance between cartilage production and degradation in the ECM?

A

The balance is regulated by enzymes and signalling pathways involved in ECM synthesis and breakdown.

38
Q

What are lacunae, and how do they form during ossification?

A

Lacunae are cavities that form when chondrocytes die and leave spaces in the cartilage matrix during endochondral ossification.

39
Q

What are the main signalling pathways involved in cartilage and bone formation?

A

Hedgehog signalling and PTHrP-mediated pathways play critical roles in regulating chondrocyte proliferation and differentiation.

40
Q

How does Sox-9 influence the development of cartilage?

A

Sox-9 activates the expression of collagen type II (Col2A) and promotes chondrocyte differentiation and ECM production.

41
Q

What is the role of TGF-β in cartilage development?

A

TGF-β supports chondrocyte proliferation and stimulates ECM synthesis, contributing to cartilage formation.

42
Q

What is the function of osteoblasts in endochondral ossification?

A

Osteoblasts replace cartilage with bone matrix, contributing to the formation of long bones.

43
Q

How does the ECM influence cell polarity and migration?

A

The ECM provides physical and chemical cues that guide the orientation (polarity) and movement (migration) of cells.

44
Q

What is the role of IHH in long bone formation?

A

Indian Hedgehog (IHH) regulates PTHrP production, ensuring proper spatial organisation and timing of chondrocyte differentiation.

45
Q

How does Hedgehog signalling regulate gene expression in cartilage development?

A

Hedgehog proteins inhibit the repressor proteins, allowing the activation of genes essential for chondrocyte function and proliferation.

46
Q

What are morphogens, and why are they important in skeletal development?

A

Morphogens are signalling molecules that control tissue patterning by guiding the spatial arrangement of chondrocytes and other cells.

47
Q

How does fibrocartilage provide support in areas of high stress?

A

Its high collagen content and low cell density make it the strongest and least flexible type of cartilage, ideal for load-bearing structures.

48
Q

Why is elastic cartilage more flexible than other types of cartilage?

A

Elastic cartilage contains a higher concentration of elastin, allowing it to return to its shape after deformation.

49
Q

What happens during cartilage catabolism in ossification?

A

Cartilage is broken down and replaced with calcified bone matrix during the ossification process.

50
Q

What is the composition of the osteoid ECM in bone?

A

It contains hydroxyapatite (a mineral) and collagen, providing rigidity and tensile strength.

51
Q

How does the avascular nature of cartilage affect its healing?

A

The lack of blood vessels limits the delivery of nutrients and repair cells, making cartilage slow to heal.

52
Q

What causes hypoxic conditions in cartilage?

A

The absence of blood vessels (avascularity) creates low oxygen conditions, which chondrocytes adapt to by relying on anaerobic metabolism.

53
Q

Why is chondrocyte metabolism adapted to hypoxic environments?

A

Chondrocytes rely on anaerobic pathways because the avascular cartilage ECM cannot deliver sufficient oxygen.

54
Q

What is the significance of the cartilage model in fetal development?

A

The cartilage model serves as a template for bone formation during endochondral ossification.

55
Q

How does PTHrP prevent premature differentiation of chondrocytes?

A

PTHrP maintains chondrocytes in a proliferative state, delaying their terminal differentiation into osteoblast-like cells.

56
Q

What is the role of glycosaminoglycans (GAGs) in the ECM?

A

GAGs attract water, forming a gel-like structure that provides resistance to compressive forces.

57
Q

What is the relationship between IHH and PTHrP in bone development?

A

IHH stimulates PTHrP production, creating a feedback loop that maintains cartilage production and chondrocyte proliferation.

58
Q

How does collagen biosynthesis affect cartilage integrity?

A

Proper collagen biosynthesis is essential for maintaining the tensile strength of the cartilage matrix.

59
Q

What is the function of chondrocyte-secreted type II collagen in cartilage?

A

Type II collagen provides structural support and tensile strength to the ECM.

60
Q

How do proteoglycans contribute to the biomechanical properties of cartilage?

A

By forming a hydrated gel, proteoglycans resist compressive forces and maintain tissue elasticity.

BMS2002: Cell Biology and Disease immunology (20 decks)

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