1 Bone and Cartilage - Structure and Function

Question 1

Describe Cartilage

Answer 1

Cartilage is specialised connective tissue

- with a support function (often shock absorbers of the body, can be tough or flexible depending on the composition)

Question 2

What are the cells that makeup Cartilage

Answer 2

Chondrocytes

Question 3

What is the matrix made of in Cartilage?

Answer 3

• Type II collagen
• Proteoglycans
  and others (depending on the type of cartilage)

Question 4

Describe Cartilage cells

Answer 4

Chondrocytes
- are derived from Embryonic Mesoderm (spindle) - clusters of chondroblasts (rounded), surrounded by a layer of perichondrium (mesenchyme derived fibroblastic cells and collagen)

Growth of cartilage is by:

• interstitial growth (a limited division of chondroblasts in ECM) AND
• Appositional growth (new chondroblasts from perichondrium)

After matrix deposition, cells become less active and become maintaining cells (lacuna is an artefact)

Question 5

Describe the ECM of cartilage (Fibres and Ground substance)

Answer 5

Made of Type II Collagen and ground substance
- Matrix is 70% water

Has Proteoglycan aggregates
- which contain glycosaminoglycans (GAGs)

Question 6

Describe the proteoglycans found in the ECM of cartilage

Answer 6

Proteoglycan aggregates
- proteoglycan monomers that are attached to a molecule of Hyaluronin - it is hydrophilic (brings in water)

This provides compressive strength
- as a flexible cushioned surface

Question 7

Describe the glycosaminoglycans that are found in the proteoglycan in ECM

Answer 7

Proteoglycans contain numerous GAGs
- attached to a core protein (bottle-brush structure - negatively charged chains)

GAG - appear in different forms

• chondroitin-4-sulfate
• chondroitin-6-sulfate
• Keratan sulfate

It is woven with collagen to form an elastic and compressible structure

Question 8

Describe the different types of Cartilage

Answer 8

It is dependent on the requirements of tissue:

• Hyaline cartilage: Type II collagen only - smooth glistening (glassy) articular surface
• Elastic cartilage: type II collagen + elastin (ear, nose, epiglottis)
• Fibrocartilage: Type I and II collagen (strong, where bones join); e.g. manubrioclavicular joint

Question 9

Describe the cellular structure of Hyaline cartilage

arrangement of cells, perichondrium, and location

Answer 9

Hyaline

• Chondrocytes are arranged in groups in a matrix
• with Type II collagen

Perichondrium
- Usually present, except at Articular surfaces

Locations
- Articular ends of long bones, ventral rib cartilage, tracheal rings

Question 10

Describe the cellular structure of Elastic Cartilage

arrangement of cells, perichondrium, and location

Answer 10

Elastic

• chondrocytes compacted in the matrix
• containing Type II collagen and elastic fibres

Perichondrium
- present

Locations
- Pinna of ear, auditory canal, laryngeal cartilages, epiglottis

Question 11

Describe the cellular structure of Fibrocartilage

arrangement of cells, perichondrium, and location

Answer 11

Fibrocartilage

• chondrocytes arranged in rows in a matrix
• containing Type I collagen bundles in rows

Perichondrium
- absent

Locations
- IV discs, pubic symphysis, joint capsules, ligaments and tendons

Question 12

Describe hyaline cartilages at joints

Answer 12

• Resists compression due to elasticity and stiffness of proteoglycans
• Tensile strength due to collagen and hydrogel ground substance
• Most are avascular - limits repair and regeneration

Nutrition is by diffusion: limits thickness (it is thin, avascular, so needs nutrients still)

• Articular surfaces of joint has no perichondrium - no source of new chondroblasts (reduces repairability)
• Cartilage atrophy is reversible - but it takes a long time

Question 13

Describe Bone as a specialised connective tissue

Answer 13

• Structurally strong - mechanical support and proctection
• reservoir for calcium and phosphate in the body
  (role in calcium homeostasis)
• Supports haematopoiesis - bone marrow

Composed of cells and ECM

• Matrix must be strong enough to support the body, yet light enough to be moved (max strength, low weight)
• The cells produce, mediate, maintain and remodel the matrix

Question 14

Describe the organisation of bone

Answer 14

• Dense outer shell - compact bone
• Inner spongy/cancellous bone - arranged in interconnecting trabecular with spaces for bone marrow

Max strength, less weight

Question 15

Describe the organisation and structure of the interconnecting trabecular system of the inner spongy/cancellous bone

Answer 15

Within a single trabecular, there are:

• concentric lamellae
• with osteocytes with lacunae - connected to each other via canaliculi (similar to the tissue arrangement in the osteons of compact bone)

However, unlike other osteons, trabecular do not have central canals or perforating canals containing blood or lymph vessels, and nerves.

Question 16

Describe how the vessels and nerves travel within the spongy bone

Answer 16

The vessels and nerves of spongy bone travel through the spaces between trabeculae, and do not need separate passageways

• Long vessels - Haversian system
• Branches - Volkmann’s Canal

Question 17

Describe Trabecular bone

Answer 17

It reduces weight

• provides space for marrow
• struts are arranged to provide maximum resistance to stresses
• Found in e.g. wrists, vertebrae, femoral neck

Question 18

Describe briefly the effect of osteoporosis on the bone structure

Answer 18

Osteoporosis

• Thinning of both critical and trabecular bone
• but the thin trabeculae are prone to fracture

i.e. FOOSH, hip fracture, dowager hump

Question 19

Describe the bone matrix

Answer 19

It is made up of 2 parts:

• Organic part (osteoid)
• inorganic part

Together, the tensile and compressive strength of the organic part (osteoid), partnered with toughness of the inorganic part
- the bone has composite properties that make it very tough and incompressible

Question 20

Describe the Organic part of the bone matrix (osteoid)

Answer 20

The Osteoid is produced by osteoblasts

• collagen type I
• Tensile and compressive strength
• Non collagenous proteins mediate mineral deposition

Without it, the bone is prone to weakness, and turns the bone soft

Question 21

Describe the inorganic part of the bone matrix

Answer 21

Inorganic part of the bone matrix is made up of:
- Calcium phosphate (hydroxyapatite)
- It is deposited in the organic matter
- 66% of the dry weight of bone
- Provides hardness
(without it, bone prone to shattering)

Question 22

Describe the bone cells found in the bone

Answer 22

Bone cells

• derived from mesenchymal stem cells
• they differentiate into osteoprogenitor cells or chondroblasts
• then, osteoprogenitor cells differentiate into osteoblasts

Question 23

What are osteoblasts?

Answer 23

Osteoblasts lay down the organic bone matrix
- and they mediate the mineralisation of the osteoid

Osteoblasts become osteocytes when surround by mineralised bone

Question 24

What are osteocytes?

Answer 24

Osteocytes maintain the matrix

- they are formed from osteoclasts, when surrounded by mineralised bone

Question 25

Describe the mineralisation of the osteoid

Answer 25

Osteoblasts secrete collagen and matrix vesicles - Matrix vesicles contain enzymes and proteins to control the availability of calcium and phosphate, so that the mineral is precipitated

Question 26

Describe the Immature osteoid (the formation and structure)

Answer 26

Woven bone - haphazard - fibre arrangement - mechanically weak - foetal development/fracture repair (rapid osteoid formation)

Question 27

Describe Mature osteoid (the formation and structure)

Answer 27

Lamellar bone - remodelled woven bone - regular parallel collagen - strong, all adult bone - arranged as osteons (aligned with the direction of force)

Question 28

Describe Mature lamellar bone

Answer 28

Concentric circles can be seen - ground bone - between 2 plates - Here, in the middle of the concentric circles, there is a Haversian canal, with osteocytes surrounding them - There are also the canaliculi (connect different cells; allow nutrients to flow

Question 29

Describe the role of Osteocytes

Answer 29

They are mature osteoblasts - and surrounded by mineralised matrix - Long cytoplasmic processes connecting to each other and osteoblasts (via gap junctions) - They maintain matrix - no osteocytes; matrix is reabsorbed In lacunar surrounded by extracellular bone fluid, that allowed nutrient diffusion through the bony channels (canaliculi) - stress information: responsive to tiny currents generated when bone is deformed - connected to both osteoblasts and osteoclasts

Question 30

What are osteoclasts?

Answer 30

They exist to destroy bone - It is a bone absorbing cells - A phagocytic cell from monocyte macrophage cell line - Multinucleate mobile cell, which attaches to the bone surface and resorbs bone leaving a pit behind (Howships lacuna) They work with osteoblasts to regulate to: - REGULATE BONE TURNOVER AND REMODELLING

Question 31

Describe how osteoclasts destroy bone

Answer 31

Large multinucleate cells - Actin clear zone zone and interns adheres it to the bone surface - Ruffled border increases surface area of the cells - Mineral is dissolved by acids; outside of cells is low pH - Lysosomal enzymes resorb organic matrix

Question 32

Describe what could affect the number of osteoclasts/function

Answer 32

Number and function is affected by PTH (parathyroid hormone) - inhibition of osteoblasts leads to - increase in the function of osteoclasts - regulate calcium level and calcitonin (does opposite) Oestrogen also reduces activity (in menopause) - keeps calcium in the bone (protects this - lack of steroid hormone may lead to osteoporosis)

Question 33

Describe bone remodelling

Answer 33

Bone is constantly remodelled through the coordinated actions of osteoblasts, osteocytes, and osteoclasts, to adjust the stresses and strains - it affects density, orientation, and responds to micro-fractures and wear and tear - AND keeps bone healthy The aim is to place bone struts at the location and direction of maximum stress, - while keeping the structure open to minimise weight

Question 34

Describe why and how bone remodelling can increase

Answer 34

In adults. bone turnover is slower than in children, but can increase due to: - change in function (onset of wailing) - New demands (running, tennis, jumping) - Repair of fractures - Disease (e.g. Paget's disease)

Question 35

Describe Osteoporosis

Answer 35

A rare group of inherited conditions - Reduced osteoclastic activity (defective bone remodelling) Osteoclasts cannot excrete H+ ions to dissolve bone mineral (H+ needed for the acidic environment) - Dense 'stone bone' but brittle and easily fractured Clinical effects: - Fractures, spinal nerve compression (excess bone) and recurrent infection (reduced bone marrow capacity), Hepatosplenomegaly due to haematopoiesis outside of the bone Potential treatments: - bone marrow transplant needed to provide healthy osteoclast precursors - can be effective

Question 36

Describe the relationship between osteoclasts and osteoblasts

Answer 36

PTH (parathyroid hormone) stimulates bone resorption by osteoclasts activation - the receptors for PTH are located on osteoblasts - Osteoclast precursors have RANK (receptor activator of Nuclear Factor Kappa B) receptor on cell membranes - Osteoblasts have the ligand for this receptor on their cell membranes (RANKL) PTH up-regulates RANKL which binds to RANK and stimulates the differentiation of osteoclasts - Osteoblasts also produce Osteoprotegrin, which prevent resorption by binding to RANKL (covering receptors; preventing binding to RANK) The ratio of RANKL:osteoprotegrin determines bone resorption (which sit on the surface of osteoblasts, which then are presented to osteoclast precursor)