24. Supplement of Cartilage and Bone

Question 1

3 types of cartilage

Answer 1

• hyaline
• elastic
• fibrous

Question 2

Explain hyaline cartilage

Answer 2

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

Question 3

Explain elastic cartilage

Answer 3

• histology and matrix similar to hyaline
• but matrix contains elastic fibres too/elastin
• chondrocytes arranged between fibres
• ear (pinna and ear canal), epiglottis

Question 4

Explain fibrous cartilage

Answer 4

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

Question 5

3 mechanisms of bone formation

Answer 5

• endochondral ossification
• intramembranous ossification
• sutural ossification

Question 6

Explain endochondral ossification

Answer 6

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

Question 7

Explain intramembranous ossification

Answer 7

• bones made directly by osteoblasts that differentiated from mesenchymal stem cells
• e.g flat skull bones, facial bones, mandible, maxilla

Question 8

Explain sutural ossification

Answer 8

• similar to intramembrous ossification but with fibrous connection
• providing stability during growth
• e.g postnatal growth of skull bones

Question 9

Embryonic origins of the skeleton

Answer 9

• trunk axial skeleton
• appendicular skeleton
• skull bones
• facial bones

Question 10

Explain trunk axial skeleton

Answer 10

• derived from schlerotome part of mesodermal somites
• endochondral ossification

Question 11

Explain appendicular skeleton

Answer 11

• derived from lateral plate mesoderm
• endochondral ossification

Question 12

Explain skull and bones embryonic origins

Answer 12

• roof and base - derived mesoderm or neural crest cells
• skull roof - intramembranous ossification
• skull base - endochrondral ossification

Question 13

Facial bones as embryonic orgins

Answer 13

• derived from neural crest cells
• intramembranous ossification

Question 14

Development of endochondral bones

Answer 14

• early perichondrium is formed by chondroblasts that are derived from condensed mesenchymal cells
• cartilage model assumes shape of future bone and perichondrium becomes prominent
• in diaphysis region, the perichondrium becomes a 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/clasts. Formation of primary ossification centre
• bone trabeculae are formed and link to bone collar
• secondary ossification centre are established in epiphysis

Question 15

In endochondral bones, growth in length is from … and growth in thickness is …

Answer 15

• epiphyseal growth plate
• periosteum

Question 16

Layers of epiphyseal/growth plate of growing endochondral bones

Answer 16

• resting chondrocytes
• proliferating chondrocytes
• prehypertophic chondrocytes
• hypertophic chondrocytes
• calcification zone

Question 17

What are resting chondrocytes?

Answer 17

• resevoir of chondrocytes
• to replenish lost chondrocytes

Question 18

What are proliferating chondrocytes?

Answer 18

• chondrocytes align in columns and divide
• secrete cartilage matrix, collagen type II

Question 19

What are prehypertrophic chondrocytes?

Answer 19

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

Question 20

What are hypertrophic chondrocytes?

Answer 20

• fully matured chondrocytes
• eventually die by apoptosis

Question 21

What is the calcification zone?

Answer 21

• cartilage matrix being replaced by osteoblasts

Question 22

How are endochondral bones mineralised?

Answer 22

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

Question 23

How to intramembranous bones develop?

Answer 23

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

Question 24

Development of sutural bones

Answer 24

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

Question 25

Define ‘sutures’

Answer 25

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

Question 26

Organisation of suture

Answer 26

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

Question 27

Histological sequence of suture

Answer 27

• bone
• cells
• fibres
• cells
• bone

Question 28

Steps of molecular control of skeletal development

Answer 28

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

Question 29

Explain 1st step of control of skeletal development - induction of mesenchyme

Answer 29

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

Question 30

Explain 2nd step of control of skeletal development - condensation of cells

Answer 30

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

Question 31

Explain 3rd step of control of skeletal development - cell differentiation programme

Answer 31

• express Sox9 - chondroblasts - cartilage matrix proteins Col II, Col X - perm or temp cartilage
  OR
• express Runx2 - osteoblasts - bone matrix proteins Col I, Opn, Ocn - intramembranous or endochondral bone

Question 32

Explain 4th step of control of skeletal development - endochondral ossification

Answer 32

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

Question 33

Molecular control of endochondral bone formation

Answer 33

• PTHrP secreted by perichondrium and periarticular chondrocytes
• induces chrondrocyte proliferation, 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 stimulates osteoblasts of bone collar

Question 34

Molecular control of intramembranous bone formation

Answer 34

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