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MSK Formative 1 > Bone and Cartilage > Flashcards

Bone and Cartilage Flashcards

1
Q

Endochondral ossification make up the bonesof ?

A
  • axial skeleton
  • appendicular skeleton
  • base of skull
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2
Q

Process of bone formation in endochondral ossification?

A
  • Cartilaginous model of bone is first made by chondrocytes
  • Osteoclasts and osteoblasts later replace this with woven bone—>
  • then remodel to lamellar bone
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3
Q

Membranous ossification make up which bones?

A

Calvarium and facial bones (skull).

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4
Q

Process of bone formation in membranous ossification?

A
  • Woven bone is formed directly without cartilage.
  • Later is remodeled to lamellar bone
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5
Q
  • Osteoblasts function?
  • Osteoblasts differentiate from?
A
  • Builds bone by secreting collagen and catalyzing mineralization in alkaline environment via ALP
  • Differentiates from mesenchymal stem cells in periosteum
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6
Q
  • Osteoclasts function?
  • Osteoclasts differentiate from?
A
  • Dissolves bone by secreting H+ and collagenases
  • Differentiate from a fusion of monocyte/macrophage precursors
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7
Q

Organic matrix is important to strength of bone. What is matrix made up of?

A
  • Over 90% collagen fibers
  • ground substance
    • mainly proteoglycans, chrondroitin sulfate and hyaluronic acid
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8
Q

Bone composition is 30%__ and 70%__?

A
  • 30% matrix
    • cells maintain and produce matrix
    • extracellular component of bone
      • 35% osteoid (organic)
      • 65% mineral (inorganic)- hydroxyapatite
  • 70% salts
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9
Q

What is the major component of bone salts?

A
  • Hydroxyapatite (form of calcium phosphate)
  • inorganic
  • important in deposition of Ca
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10
Q
  • Collagen in bong is along lines of?
  • Important for?
A
  • Along lines of tensional force
  • Important to tensile strength
  • Has high compression strength so bone resists both tension and compression
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11
Q
  • Extracellular matrix forms most of what kind of tissue
  • What is important to density and deformability of matrix?
A
  • Forms bulk of connective tissue
  • Hydration is important!
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12
Q

What are the functions of ECM?

A
  • Provides structure and support
    • (holds cells and tissues together)
  • Limit movement and migration
  • barrier to microorganisms and large molecules
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13
Q
  • What is the most abundant type of protein in the body, especially which form?
  • Found in?
A
  • Collagen 1
  • found in:
    • loose connective tissue,
    • bone
    • tendons,
    • skin
    • blood vessels
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14
Q

Structure of collagen? What does it need to stabilize it?

A
  • Triple helix with repetitive nature
  • needs vitamin C to stabilize
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15
Q
  • Lack of Vitamin C means less stability of __?
  • Symptoms of Scurvy?
A
  • Less stability of collagen and tissues where it is important
  • Skin less stable, blood vessels easily injured, gums less stable so teeth are loose
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16
Q
  • Collagen IV makes a __ rather than fibrils.
  • Important in which structures?
A
  • Makes a mesh
  • important in basement membranes and basal lamina
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17
Q
  • Glycosaminoglycans (GAG) are repeating __ units with?
  • Which glycosaminoglycan is the backbone of the matrix?
A
  • Repeating disaccharide units
  • Hyaluronic acid (just disaccharide units)
    • bind HA to proteoglycans
    • Negative charges bind positive ions,
    • H+ bonds to water to form hydrated gel
    • matrix is flexible and acts a filter
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18
Q

How is cartilage able to be compressed and deformable/regain shape after pressure is released?

A
  • High number of negative charges attract cations,
  • create high osmotic pressure water drawn in,
  • tension balances at swelling equilibrium
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19
Q

Function of fibronectin in the matrix?

A
  • Proteoglycans bind to fibronectin (besides HA)
  • Fibronectin binds to integrins in cell membranes
    • collagen fibrils cells attached to all matrix components
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20
Q

How is bone matrix degraded?

A
  • Components (GAG) enter cells by endocytosis and fuse with lysosomes
  • lysosomal hydrolase break these down into sugars and amino acids
    • lack of any enzyme will prevent degradation and accumulation of partially degraded material in lysosome
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21
Q
  • Stem cells in bone respond to ___ from osteoblasts?
  • These precursors then become osteoclasts that respond to__ and __?
A
  • M-CSF from osteoblasts
  • precursors become osteoclasts
    • responding to IL-6 and RANKL;
    • important in osteoclast regulation and bone remodeling/resorption
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22
Q
  • Osteoclasts are regulated by __ and __?
  • What do osteoclasts release against bone surface?
A
  • Cytokine receptors (stimulate resorption)
  • Calcitonin (inhibit resorption)

Release H+ ions, phosphotases (TRAP) and lysosomal enzymes

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23
Q
  • Integrins are?
  • What type of signals to they transmit?
A
  • Transmembrane proteins (alpha-beta dimers)
  • connect to matrix and cytoskeleton
  • Pass physical signals across cell membrane
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24
Q

Role of matrix maetalloproteinasees (MMPs) in degradation of ECM proteins?

A
  • MMP degrade all ECM proteins (locally)
    • Important for migration and remodeling
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25
Q

Regulation of MMPs in degredatin of ECM proteins?

A
  • Synthesized with propeptide that must be cleaved to activate
  • TIMP (Tissue Inhibitors of Malloproteinases)
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26
Q

On which cells in the bone are the RANK receptor and ligand located?

A
  • RANK ligand on osteoblast/stromal cell
  • RANK receptor on osteoclast precursor
    • Need RANK and M-CSF (always floating around) to differentiate into osteoclast
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27
Q

What binds to the RANK ligand on osteoblast/stromal cells and inhibits it’s interaction with RANK receptor on osteoclast precursor cells?

A
  • Osteoprotein (OPG) prevents differentiation into osteoclast
    • acts as a decoy for RANKL
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28
Q

What are other ECM proteins that are not important in bone but are important in skin and other tissue?

A
  • Laminin
    • Binds collagen to ECM molecules and cell integrins to provide stability
  • Elastin
    • allows blood vessels to deform, lungs to expand and contract without energy
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29
Q

Where is elastin found?

A

Abundant elastic fibers found in:

  • smooth muscle endothelium near chondrocytes and fibroblast
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30
Q
  • Chrondroblasts form from which cells?
  • Where are they abundant?
A
  • Form from mesenchymal cells
  • Abundant in the perichondrium
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31
Q
  • Chondrocyte is defined when?
  • What do chondrocytes secrete?
  • Abundant in?
A
  • Defined when chondroblasts are surrounded by the “matrix” they produce
    • Sit in lacunae
  • Secrete Type II collagen and extracellular matrix
  • Abudant lipids, glycogen and RER
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32
Q

Extracellular matrix (“ground substance”) consits of?

A
  • Hyaluronic acid
  • glycosaminoglycans
    • chondroitin sulfate
    • keratin sulfate

It is extremely hydrated

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33
Q
  • Pericellular matrix has the highest concentration of?
  • What type of collagen surrounds each chondrocyte?
A
  • highest [] of sulfated proteoglycans, hyaluronic acid and glycoproteins
  • Type VI collagen surrounds each chondrocyte
34
Q

What does territorial matrix consist of?

A

Type II collagen and proteoglycans

35
Q
  • What parts of the body is comprised of hyaline cartilage?
  • What does it serve as?
A
  • Nasal, laryngeal, costal and tracheal cartilage
  • Articular cartilage
  • Fetal skeleton

Serves as shock abosorber

36
Q

What is hyaline cartilage composed of?

A
  • Cells (chondrocytes and chondroblasts)
  • Type II collagen fibers (mostly)
  • Extracellular matrix
    • hyaluronic acid, proteoglycans and water
37
Q

Chondrogenesis:

  • Appositional growth?
  • Interstitial growth?
A
  • Appositional growth:
    • new cartilage formed from inner surface of perichondrium
  • Intersitial growth:
    • new cartilage formed from within cartilage
38
Q
  • Where is fibrocartilage found?
  • Characterized by?
A
  • Found in:
    • intervertebral disk
    • menisci of knees
    • TMJ
    • sternoclavicular joints
    • pubic symphis
  • Characterized by great tensil strength
39
Q

Fibrocartilage is comprised of?

A
  • Chondrocytes and firbroblasts
  • Type I and Type II collagen
    • less water and proteoglycans than hyaline cartilage
40
Q

Annulus fibrosis and Nucleus pulposus (intervertebral disk) are made of?

A
  • Annulus fibrosis
    • fibrocartilage
  • Nucleus pulposes
    • Physaliphorous cells and extracellular matrix of ground substance (squishy)
41
Q
  • Where is elastic cartilage found?
  • Abundant in?
  • Characteristics?
A
  • In external ear, epiglottis and auditory tube
  • Abudant type II collagen and elastic fibers in ECM
  • Elastic and pliable
42
Q

What makes articular cartilage different from general hyaline cartilage?

A
  • No perichondrium (contacts bone directly)
  • Obliquely oriented collage matrix in transition zone
  • Longitudinally oriented collage fibrils in the deep zone
43
Q

T/F:

  • Cartilage repairs easily
A
  • False!
    • cartilage is not very capable of repair
    • avascular
44
Q
  • What does perichondrium have that relates to repair?
  • When damage is repaired what happens to hyaline cartilage?
A
  • Perichondrium has pluripotent stem cells
    • but type II collage is very stable
  • When damage is repaired, hyaline cartilage is converted to mixture of hyaline and fibrous cartilage
    • mix of type I and II cartilage
  • Damaged cartilage may even be converted to bone (normal with aging)
45
Q

Lamellar bone

A

Mature bone with lamellae (overlapping folds)

46
Q

Woven bone?

  • Common in?
A

Developing or immature bone

  • Fetus or fracture
47
Q
  • Compact bone is defined by?
  • Where is it found?
A
  • Defined by osteons (Haversion system)
  • Solid bone found in outer protions of shaft of long bones
48
Q
  • Spongy/Cancellous bone found toward?
  • Lamellated but no?
A
  • Bony spicules and trabeculae found toward the marrow space and in the metaphyses
  • Lamellated but NO Haversion system
49
Q

Bone matrix is composed of:

  • Organic
  • Inorganic

What is in each?

A

Organic:

  • Type I collagen, proteoglycans, chondroitin sulfate, keratin sulfate, hyaluronic acid
  • Multiadhesive glycoproteins

Inorganic

  • Hydroxyapatite (caclium phosphate)
50
Q

Long bone is composed of:

  • Periosteum: inner and outer layer
  • Sharpey’s Fibers
  • Lamallae
A
  • Periosteum
    • _Outer laye_r: collagen fibers and blood vessels
    • I_nner laye_r: osteoprogenitor cells and osteoblasts
  • Sharpey’s fibers:
    • collagen fibers to the outer circumferential lamellae
  • Lamallae
51
Q
  • In corticol (compact) bone which way do each run? What are they surrounded by?
    • Haversian canals
    • Volkmann canals
A
  • Haversion canals run longitudinal
    • ​surrounded by concentric lamellae
  • Volkmann canal runs transverse
    • transversely connect to Haversion system and to the periosteum
52
Q
  • In compact bone where is Endosteum vs. Periosteum?
  • What does it contain?
A
  • Osteoprogenitor cells
  • osteoblasts
  • reticular fibers
53
Q

Where do osteocytes sit?

A

In lacunae (trapped osteoblasts)

54
Q

Osteoid contain?

A

Type I collagen and proteoglycans

55
Q

Osteoblasts contain abundant RER to produce?

A
  • Osteocalcin
    • mediates bone mineralization via Ca2+ binding
  • Osteonectin
    • brindges collages and minerals (hydroxyapetite)
  • Alkaline phosphotase
  • Osteoid
    • ​secrete Type 1 collagen
  • pyrophosphatase
56
Q

Where are osteoclasts multinucleated?

A

merging of monocytes and macrophage progenitor cells in BM

57
Q

What do osteoclasts secrete?

A
  • Acid
    • degrade minerals in bone
  • Lysosomal proteins
    • degrade collagen and non collagen proteins
  • Metalloproteinases (MMP)
    • degrade collagen and non collagen
58
Q

Osteoclasts are regulated by?

A
  • PTH:
    • stimulates RANKL on surface of osteoblasts
    • RANKL interacts with receptors on surface of osteoclasts and encourage bone resorption
59
Q

Role of pyrophosphate and alkaline phosphate in bone?

A
  • Pyrophosphate:
    • controls (inhibits) mineralization
  • Alkaline phosphotase:
    • neutralizes pyrophosphate
60
Q
  • Intramembranous ossification is important for the development of which bones?
  • What does bone arise from?
A
  • Development of frontal, parietal, occipital and temporal bone (skull) as well as mandible and maxilla
  • Bone arises from primitive mesenchymal connective tissue (NOT from cartilage)
    • mesenchymal cells give rise to osteoblast
    • bone formed within a “blastemal” lined by osteoblasts
61
Q

Endochondral ossification is important for the development of which bones?

A
  • Extremities
  • Vertebral column
  • Pelvis
62
Q
  • MOA of Endochondral ossification?
  • Primary vs. Secondary ossification center?
A
  • Chondroblasts lay down Type II collagen initially but then Type X cartilage
  • Primary ossification center:
    • form a periosteal collar of bone after apoptosis and calcification of matrix at the diaphysis
  • Secondary ossification center
    • forms at the epiphysis

Vascularization helps promote entrance of osteoprogenitor and hematopoietic cells

63
Q

In bone what is happening in:

  • zone of reserved cartilage
  • zone of proliferation
A
  • Zone of proliferation:
    • reserve of chondrocytes
  • Zone of proliferation:
    • continuous cell division
    • chondrocytes align as vertical and parallel columns
64
Q

In bone, what is happening in:

  • zone of hypertrophy
  • zone of calcified cartilage
  • zone of resorption
A
  • zone of hypertrophy
    • chondrocytes swell up with collagen
    • are hypertrophic chondrocytes because of glycogen
      • secrete more Type X collagen as well as VEGF
  • Zone of Calcified Cartilage:
    • _​_Chondrocytes become calcified
      • promote apoptosis because diffusion of nutrients to cell is diminished
  • Zone of resorption:
    • _​_proliferation of osteogenic cells and vascular invasion
65
Q
  • Mechanism of fracture repair and bone healing?
A
  • Begins with deposition of highly vascular collagenous granulation tisssue
  • Chondroblasts develop to replace granulation tissue with hyaline cartilage
    • provisional soft callus
  • Osteoprogenitor cells from endosteum and periosteum go to work to create woven bone (hard)
  • Woven bone gradually replaced with lamellar bone via remodeling
66
Q
  • Articular cartilage at the bony end plate has no?
  • What is it separated from cartilage by?
A
  • NO Haversion systems and canaliculi
  • Separated from cartilage by a glycoprotein rich substance
    • similar to cement lines
67
Q
  • What is the synoviam?
  • What does it contain?
A
  • Outer layer of dense connective tissue (in joint capsule)
  • Inner synovial membrane with 1-2 layers of synovial cells
    • NO basement membrane
    • NO tight junctions
    • Fenestrated capillaries
68
Q
  • Tendons are composed of?
  • Where tendons insert into bones there is no?
A
  • Composed of dense regular connective tissue
    • regularly oreinted parallel bundels of collagen fibers separated by rows of fibroblasts
  • NOTE:
    • ligaments secure bones and joints but have a less orderly arrangement of collagen fibers
  • Where tendon inserts into bone there is no periosteum
69
Q
  • Osteoid, the organic component of bone matrix is made of?
A
  • Mostly Type I collagen
  • Osteopontin/ Osteocalcin: only protein unique to bone
    • produced by osteoblasts
    • function in bone mineralization, Ca homeostasis
  • Cytokine and growth factors
    • control bone cell proliferation, maturation and metabolism
  • Glycosaminoglycans
70
Q

Osteoprogenitor cells are what kind of cells?

A

Pluripotent mesenchymal stem cells located at bone surface

71
Q
  • When do osteoblasts become osteocytes?
  • What is function of osteocytes?
A
  • Osteoblasts become osteocytes when they are embedded within the matrix
  • Osteocytes function to:
    • communicate with each other and other bone cells via cytoplasmic process tunnels (canaliculi)
    • control Ca and P levels in locally
    • Mechanotransduction
72
Q

How do osteoclasts perform bone resportion?

A
  • Bone resorption:
    • attach to matrix with cell surface integrins to create a sealed extracellular trench (resorption pit)
    • secrete proteases into the pit to disolve matrix components
73
Q

Osteoclasts differentiate by cytokines and growth factors, produced by osteoblasts, including?

A
  • M-CSF (macrophage colony stimulating factor)
  • IL-1
  • TNF
74
Q
  • RANKL on osteoblast promote?
  • OPG on osteoblast promote?
A
  • RANKL promote bone resorption
    • ​bind to RANK of osteoclast precursor and promote differentiation
    • Enhanced by binding of M-CSF to receptor
  • OPG (Osteoprotegrin) promote bone formation
    • acts as decoy receptor for RANKL
    • inhibit osteoclast differentiation and resorption
75
Q

Explain the process of paracrine cross talk between osteoblasts and osteoclasts?

A
  • As bone is resorbed, factors are released (matrix proteins, GF, etc.) locally and stimulate osteoblast
    • initiate bone renewal
  • Osteoprogenitor cells produce WNT and BMP
    • bind to receptors on osteoblasts and increase production of OPG
      • promote bone formation
76
Q

Senile osteoporosis is related to?

A
  • Age related changes
    • decreased proliferative and biosynthetic potential
    • decrease response to GF
    • net result: diminished capacity to make bone
77
Q

Through what process does physical activity stimulate bone growth?

A
  • Mechanical forces stimulate normal bone remodeling: Mechanotransduction
    • strain/pressure of muscle contraction is transmitted to osteocytes through fluid in canaliculi
    • mechanical signal stimulates secretion of factors that increase bone remodeling
      • stimulate osteoblast differentiation and activity
      • decrease osteoclast activity
    • result: positive bone balance
78
Q

How does a decrease in estrogen lead to postmenopausal osteoporosis?

A
  • Decrease estrogen stimulates blood monocytes and bone marrow cells to secrete inflammatory cytokines
  • Increase RANKL and decrease OPG
    • increase osteoclast recruitment and activity
    • decrease osteoclast apoptosis
  • Resorption>formation
79
Q

MOA of Vitamin D hormone?

A
  • Binds a nuclear receptor (vitamin D receptor, VDR) which associates with RXR to form a heterodimer
  • Heterodimer binds to vitamin D response element (VDRE)
80
Q

What is the result of Vitamin D deficiency?

A
  • Impaired mineralization and accumulation of unmineralized matrix
  • Can cause Rickets (children) and Osteomalacia (adults)
81
Q

Compare Rickets and Osteomalacia to Osteoporosis

A
  • Osteoporosis: mineral content is normal but total bone mass is decreased
  • Rickets: decreased bone deposition in growth plate of developing bone
  • Osteomalacia: bone formed during remodeling is undermineralized resulting in predisposition to fractures
82
Q

How can you differentiate between osteoporosis and osteomalacia?

A
  • Abnormal blood levels of Vitamin D, calcium and phosphorus
  • X-ray: slight cracks in bones
    • Looser transformation zones; characteristic in osteomalacia

MSK Formative 1 (11 decks)

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