23 A - Cartilage and Bone Supplement

Question 1

3 types of cartilage

Answer 1

• hyaline
• elastic
• fibrous

Question 2

Proporties of hyaline cartilage

Answer 2

• most common
• large chondrocytes surrounded by cartilage matrix
• mainly type 2 collagen and chondroitin sulfate (GAG)
• articulating surfaces of joints, nose, larynx, trachea and bronchi

Question 3

Colour of hyaline cartilage

Answer 3

transparent

Question 4

Properties of elastic cartilage

Answer 4

• histology and matrix similar to hyaline (large chondrocytes surrounded by cartilage matrix)
• but matrix has elastic fibres/elastin
• chondrocytes arranged between fibres
• ear (pinna and ear canal) and epiglottis

Question 5

What colour is elastic cartilage>

Answer 5

yellow

Question 6

Properties of fibrous cartilage

Answer 6

• parallel rows of smaller chondrocytes embedded between type I collagen fibre bundles
• high tensile strength, resists pressure
• intevertebral disks, TMJ, pubic symphysis

Question 7

Where is hyaline cartilage found?

Answer 7

• articulating surfaces of joints, nose, larynx, trachea, bronchi

Question 8

Where are elastic cartilage found?

Answer 8

• ear (pinna and ear canal)
• epiglottis

Question 9

Where is fibrous cartilage found?

Answer 9

• intevertebral disks
• TMJ
• pubic symphysis

Question 10

3 mechanisms of bone formation

Answer 10

• endochondral ossification
• intramembranous ossification
• sutural ossification

Question 11

Explain endochondral ossification

Answer 11

• bones made from cartilage model
• condrocytes produce hyaline cartilage that is replaced by osteoid/bone from osteoblasts
• e.g long bones (epiphyseal growth plate), mandibular condyle (secondary cartilage) and base of skull (synchondrosis)

Question 12

Explain intramembranous ossification

Answer 12

• bones made directly from osteoblasts that have differentiated from mesenchymal stem cells
• like flat skull bones, facial bones, mandible, maxilla

Question 13

Explain sutural ossification

Answer 13

• similar to intramembranous - bone directly from osteoblasts from mesenchymal stem cells
• but with fibrous connection providing stability during growth
• e.g postnatal growth of skull bones

Question 14

List embryonic origins of skeleton

Answer 14

• trunk axial skeleton
• appendicular skeleton
• skull bones

Question 15

Explain the embryonic origins of the skeleton

Answer 15

• trunk axial skeleton from sclerotome of mesodermal somites - endochondral ossification
• appendicular skeleton from lateral plate mesoderm - endochondral ossification
• skull bones - roof and base from mesoderm or neural crest cells (roof - intramembranous ossi, base is endochondral)
• facial bones from neural crest cells - intramembranous ossification

Question 16

Development of endochondral bones

Answer 16

• early perichondrium is formed by chondroblasts derived from condensed mesenchymal cells
• cartilage model assumes shape of future bone and pericondrium becomes more prominent
• in diaphysis region, perichondrium becomes periosteum. Osteoblasts differentiate from osteoprogenitor cells in periosteum and produce collar of bone (cortical bone - intramembranous)
• cartilage matrix begins to calcify (dots)
• blood vessels invade cartilage model through bone collar and introduce osteoblasts and clasts. get formation of primary ossification centre
• bone trabeculae formed and link to bone collar
• secondary ossification centre established in epiphysis

Question 17

Growth in length of endochondral bones is … but thickness is …

Answer 17

• epiphyseal growth plate
• periosteum

Question 18

Cells involved with epiphyseal growth plate

Answer 18

• resting chondrocytes
• proliferating chondrocytes
• prehypertrophic chondrocytes
• hypertrophic chondrocytes
• then calcification zone

Question 19

What are resting chondrocytes?

Answer 19

resevoir of chondrocytes to replenish lost chondrocytes

Question 20

What are proliferating chondrocytes?

Answer 20

chondrocytes align in column and divide (secrete collagen matrix, collagen type II)

Question 21

What are prehypertrophic chondrocytes?

Answer 21

• chondrocytes begin to swell
• increased production of cartilage matrix (collagen type X)

Question 22

What are hypertrophic chondrocytes?

Answer 22

• fully matured chondrocytes
• eventually die by apoptosis

Question 23

What happens in the calcification zone?

Answer 23

• cartilage matrix being replaced by osteoblasts

Question 24

Explain mineralisation of endochondral bones

Answer 24

• matrix vesicles bud off from chondrocytes and induce mineral deposition between collagen II fibres
• first hydroxyapatite crystals catalyse formation of mineralisation foci - calcified cartilage
• osteoblasts surround calcified cartilage and deposit osteoid (bone matrix) that is later mineralised to bone
• mixed spicule contains calcified cartilage and bone - chondroclasts remove cartilage

Question 25

Development of intramembranous bones

Answer 25

• mesenchymal cells in cellular periosteum differentiate to become osteoblasts which produce irregular bone type (woven bone)
• gradual turnover of woven bone to lamellar bone
• formation of primary osteons by osteoblasts surrounding blood capillary
• continued bone replacement produces highly organised, mature bone
• fewer cells, secondary and tertiary osteons, circumferential lamellae

Question 26

What colour are osteoblasts?

Answer 26

yelloe

Question 27

Development of sutural bones

Answer 27

• condensation of mesenchymal cells that form periosteum
• differentiation into osteoblasts that deposit woven bone

Question 28

What is a suture?

Answer 28

• fibrous joints between skull bones
• enable skull bone growth in response to brain growth

Question 29

How are sutures organised?

Answer 29

• cambrian layer - cellular for bone growth mediated by osteoblasts
• capsular layer - fibrous for stability mediated by fibroblasts

Question 30

Histological sequence of sutures

Answer 30

• bone
• cells
• fibres
• cells
• bone

Question 31

List molecular control methods of skeletal development

Answer 31

• induction of mesenchyme
• condensation of cells
• cell differentiation programme
• endochondral ossification

Question 32

How is induction of mesenchyme a molecular control of skeletal development?

Answer 32

• notochord to sclerotome cells
• AER to lateral plate mesoderm cells
• neural fold to local environment to neural crest cells
• inducers - WNT, BMP, FGF, SHH

Question 33

How is condensation of cells a molecular control of skeletal development?

Answer 33

• express N-cadherin (cell adhesion)
• TGF-beta signals stabilise condensation
• differentiation of osteo-chondroprogenitors

Question 34

How is cell differentiation programme a molecular control of skeletal development?

Answer 34

• express Sox9 to chondroblasts to cartilage (matrix proteins of Collagen II, X) - perm or temp endochondral cartilage
  OR
• express Runx2 to osteoblasts to bone (matrix proteins of Collagen I, Opn, Ocn) - intramembranous or endochondral bone

Question 35

How is endochondral ossification a molecular control of skeletal development?

Answer 35

• ordered chondrocyte differentiation
• IHH, PTHrP, BMP regulatory loop
• RUNX2 also induces chondrocyte hypertrophy
  OR
• VEGF secreted by hypertrophic chondrocytes induces vascular invasion - introduction of osteoblasts and clasts

Question 36

Molecular control of endochondral bone formation

Answer 36

• PTHrP secreted by perichondrium and periarticular chondrocytes
• induces chondrocyte proliferation and inhibits IHH secretion
• IHH expressed by (pre)hypertrophic chondrocytes that are out of reach of PTHrP signals - IHH directly stimulates chondrocyte proliferation
• IHH stimulates PTHrP expression - negative feedback loop, coordinated chondrocyte differentiation
• IHH also stimulates osteoblasts of bone collar

Question 37

Molecular control of intramembranous bone formation

Answer 37

• differentiation of mesenchymal stem cells into connective tissue
• osteoblast differentiation (Runx2 induces foramtion of preosteoblasts, osterix induces osteoblast differentiation - express RANKL on cell surface, secrete osteoprotegerin)
• osteoclast differentiation (M-CSF induces formation of preosteoclasts from hematopoietic stem cells - express RANK of cell surface - RANKL/RANK interaction induces fusion of preosteoclasts to form mature osteoclasts - OPG is a decoy receptor blocking this interaction)
• coordination of bone formation and resorption