Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MSS > MSS06 Biochemistry Of Cartilage And Bone > Flashcards

MSS06 Biochemistry Of Cartilage And Bone Flashcards

1
Q

Tissue homeostasis

Context - Form - Function

A
  1. Extracellular matrix components
    - collagen
    - proteoglycan
    - glycoprotein
  2. Cell-matrix interaction / communication
    - integrins
    - fibronectin
  3. Matrix degradation / remodelling
    - matrix metalloproteinase (MMP)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Extracellular matrix (ECM)

A
  • mixture of proteins and glycoproteins
    —> produced by cells and surrounding the cells
  • composed of
    1. Collagen (insoluble fibres)
    2. Proteoglycan (    soluble polymers)
    3. Adhesive Glycoprotein
  • interact specifically in an architecturally-precise manner
  • take stress off movement and maintain shape e.g. bone and cartilage

Function:

  • **Modulates functions and properties of tissues
    1. Cornea: transparent
    2. Basal lamina: thin mat-like, tough
    3. Tendon: rope-like
    4. Skin/artery: strength and resilience
    5. Cartilage: shock absorbing
    6. Teeth/bone: hard

Type and organisation of the relative amounts of matrix components
—> dictates tissue function
1. Tendon
2. Cartilage
3. Dermis (fibres orientate in different direction, allow different direction of pull)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

ECM-associated degenerative disease:

A
  1. Osteoporosis
  2. Osteoarthritis
  3. Intervertebral disc degeneration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

***Bone matrix

A

Dense matrix:
- 70% inorganic, 30% organic (90% collagen)

Inorganic:
1. ***Calcium phosphate (as hydroxyapatite crystals)

Organic:
1. Mixture of tough collagen fibre
—> mainly ***Type I Collagen arranged in regular layers
—> for mineralisation and tensile strength

  1. Proteoglycans + GAGs (hyaluronan, decorin, biglycan, fibromodulin)
  2. Glycoproteins
    - Osteopontin
    - Bone sialoprotein
    - Osteocalcin and matrix Gla protein
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Type 1 collagen molecule

A

**α chain: C terminal propeptide + N terminal propeptide + Gly-X-Y repeats
—> 3 α chains (2xα1, 1xα2)
—> C terminal propeptide initiates **triple helix formation in rER
—> Procollagen secreted into extracellular space
—> Procollagen peptidase: Cleave Procollagen —> Collagen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Structural organisation of fibrillar collagen

A

***Procollagen
—> Collagen
—> Fibril

Homogenous fibrils:
—> only type 1
—> Electron dense / NOT dense area
—> ***regular banding

Heterotypic fibrils:
—> contain other types of collagen for specialised functions

***Collagen fibres are insoluble polymers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Glycoproteins in bone

A 
Characteristics feature:
***Anionic nature
—> rich in Acidic amino acids (Asp, Glu)
—> ***bind to minerals
—> involvement in the ***calcification (mineralization) process
  1. Osteopontin:
    - -ve regulator
    - stretches of consecutive Aspartic residues
  2. Bone sialoprotein:
    - +ve regulator
    - stretches of consecutive Glutamic residues
  3. Osteocalcin and matrix Gla protein:
    - +ve regulator
    - γ-carboxyglutamic acid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Prerequisites of mineralisation of bone matrix

A
  1. ***↑ Local ion concentration
  2. ***↓ Mineralisation inhibitors
  3. Formation of ***mineral nucleators
    —> sit in holes in fibrils
  4. Collagen I fibrils support ***hydroxyapatite deposition (nucleation at hole zones)
  5. Continued accumulation of hydroxyapatite
  6. ***Regulators of mineralisation
    —> e.g. Alkaline phosphatase by osteoblasts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Structure of bone

A
  1. Lamellar (compact) bone

2. Trabecular (spongy / cancellous) bone (take stress off, shock absorber)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

***Cartilage matrix components

A
  1. Cellular component:
    - Chondrocyte
  2. Fibrous component:
    - ***Collagen type II
  3. Proteoglycan (Soluble polymers):
    - ***Aggrecan, decorin, biglycan, lumincan, perlecan
    - syndecan, glypican (membrane bound)
  4. Glycosaminoglycans (GAG) (Soluble polymers):
    - ***Hyaluronic acid
    - chondroitin, heparan, keratan, dermatan sulfate
  5. Glycoprotein:
    - ***Fibronectin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Glycosaminoglycan (GAG)

A
  • family of **linear polymers comprised of repeating **disaccharides
  • (N-acetylglucosamine / N-acetylgalatosamine) + (D-glucuronidation acid / L-iduronic acid)
  • > =1 **OH groups of amine sugars esterified with **sulfate
  • **highly negatively charged
    —> attract cation
    —> **    soak up water
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Hyaluronic acid

A
  • ***Unsulphated GAG (好長)
  • Not attached to a protein core
  • single molecule up to 50000 repeating units with MW up to 10^7

Function:
1. **Resist compressive forces in cartilage
2. Forms clear and viscous **solutions —> serve as **Lubricants in synovial fluid of joints
3. **Space filler
—> change shape of structure
—> provide cell free space

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Proteoglycan

A
  • Core protein with >= 1 GAG covalently attached (牙刷仔)
  • GAG generally much shorter than hyaluronic acid
  • GAG: greater fraction, site of biological function
  • **Highly -ve charged
    —> high affinity for cation —> **    hydrophilic —> swelling pressure
    —> hydrogen bonding + electrostatic interactions

2 types:

  1. **Lecticans (much more GAG)
    - Sulphated Proteoglycan
    - **    Aggrecan, Brevican, Neurocan, Versican
  2. Short leucine repeat proteoglycans (SLRPs) (less GAG)

Other types:
- Small proteoglycan
e.g. ***Decorin, Biglycan, Lumican, Perlecan, Syndecan, Glypican
—> function as organising ECM, signaling etc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

HA and aggrecan relationship

A

HA: long chain backbone
Aggrecan (牙刷仔): attach on HA

—> forms huge aggregate that soaks water

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

***General function of proteoglycan

A
  1. Provide ***hydrated space around cells
  2. Act as selective ***sieves regulating traffic of molecules and cells (size, charge: e.g. Kidneys)
  3. Binds secreted ***signaling molecules (e.g. growth factors)
  4. Binds and regulate ***proteases and protease inhibitors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Adhesive glycoproteins

A
  • Large no. in ECM
  • Key feature: Ability to ***interact with cells and other macromolecules in ECM
  • Many have functional **peptide domains that interact with **cell surface receptors + other matrix molcules
  • Some may also involve interaction with **inorganic phase e.g. Mineralized CT: bone and dentine
    —> **    bind to minerals
    —> involvement in the ***calcification (mineralization) process
  • Example: Fibronectin
17
Q

***Fibronectin

A

Functional form: ***Disulphide bonded dimer

  1. Promote cell ***adhesion
  2. Affect cell morphology, ***migration and differentiation
  3. Bind to **cell surface via **Integrin receptors and ***Arg-Gly-Asp motif (RGD)
  4. Binds ***ECM: collagen, heparin/heparan sulphate proteglycan, fibrin
  5. Forms fibrillar matrix: further stabilized by extensive S-S
18
Q

Cartilage matrix component

A

Collagen and Proteoglycan:

  • structural support
  • shock absorption

Others:

  • regulate fibril formation
  • interactions between matrix molecules

Pericellular matrix: Glycoprotein (Fibronectin)

Territorial matrix:
Collagen, Proteoglycan (Decorin)

Inter-territorial matrix:
HA + Aggrecan

19
Q

Composition of ECM determines Structural property of tissue

A

Bone:

  • more collagen (mineralization: stronger)
  • less proteoglycan

Cartilage:

  • relatively less collagen
  • more proteoglycan (soluble polymer)
20
Q

Matrix receptors

A

Mediate interaction between cell and ECM

  • ***Integrin
  • Discoidin domain receptors (DDRs)
21
Q

Integrin

A
  • large family of ***transmembrane protein
  • Interact with **ECM (outside cell) and **cytoskeleton (inside cell)
    —> ***Transmit signals
  • Cell-matrix / cell-cell interactions are weak
    —> however hundreds group together —> form ***Focal adhesions (within the cell)
    —> Enhance specificity through multiple interactions
  • Matrix binding site
    —> α chain + β chain (Heterodimer)
    —> cysteine rich domain
    —> only binds to matrix with ***specific a.a. sequence (Arg-Gly-Asp (RGD))
    —> 1 single β chain interact with multiple α chains
    —> forms different combinations of Intergrin heterodimers
    —> diversity of integrins bind different ligands
  • Cytosolic side:
    Interact with Cytoskeleton
22
Q

ECM and cell function

A 
Interact with each other
—> Maintenance and Homeostasis
—> Any of them went wrong
—> influence each other in bad manner
—> vicious cycle

ECM homeostasis:

  • Gene expression —> Matrix assembly —> Matrix turnover —> Gene expression
  • Imbalance: degenerative disease (OA, RA, IV degeneration, osteoporosis)
23
Q

Enzymes involved in matrix turnover

A
  1. Matrix metalloproteinases (MMP)
    - Key enzyme in **matrix degradation
    - **    Collagenases, **Gelatinases, Stromlysin
    - Cleaves at specific site of ECM protein
    - Regulation of activity
    —> synthesized as inactive proenzymes
    —> regulated by **    TIMP (Tissue inhibitors of MMP)
  2. Other degradative enzymes:
    - ***Hyaluronidase, chondroitinase
24
Q

***Overview of ECM function

A
  1. Structural
    - collagen
    - proteoglycan
    - GAG
  2. Signaling
    - integrin
  3. Hold / transmit cytokines, growth factors
    - proteoglycan
    - glycoprotein
  4. Degradation
    - MMP
    - hyaluronidase
25
Q

***Summary: Cartilage vs Bone

A

Cartilage: ***much more ECM
—> Pericellular, Territorial, Inter-territorial matrix

Bone:
Dense matrix:
Inorganic (70%):
1. ***Calcium phosphate (as hydroxyapatite crystals)

Organic:
1. Mixture of tough collagen fibre
—> mainly ***Type I Collagen arranged in regular layers
—> for mineralisation and tensile strength

  1. Proteoglycans + GAGs (hyaluronan, decorin, biglycan, fibromodulin)
  2. Glycoproteins
    - Osteopontin
    - Bone sialoprotein
    - Osteocalcin and matrix Gla protein

Cartilage:

  1. Cellular component:
    - Chondrocyte
  2. Fibrous component:
    - ***Collagen type II
  3. Proteoglycan (Soluble polymers):
    - ***Aggrecan, decorin, biglycan, lumincan, perlecan
    - syndecan, glypican (membrane bound)
  4. Glycosaminoglycans (GAG) (Soluble polymers):
    - ***Hyaluronic acid
    - chondroitin, heparan, keratan, dermatan sulfate
  5. Glycoprotein:
    - ***Fibronectin

MSS (32 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions