MSS: Cellular Stucture of Bone

Question 1

List some functions of bone.

Answer 1

• support and movement, as an attachment site for muscles
• protection for internal organs
• provides a home for bone marrow
• acts as a mineral reservoir (calcium)
• collaborates with the endocrine system: is a source of some ‘non-classical’ hormones

Question 2

Describe bone structure.

Answer 2

We talk about cortical bone and trabecular bone.

Cortical bone is known as compact. It is found on the surface of bones, and is made of repeated units wrapped around each other. This results in minute, longitudinal canals that allow for blood vessel penetration.

Trabecular bone is known as spongy and cancellous. It has a less organised structure, made up of interlocking struts.

Question 3

What is the composition of bone?

Answer 3

It is 25% protein (organic osteoid matrix), and 75% minerals.

It is also made up of cells, which contribute to the weight.

Question 4

Describe the organic (osteoid) protein matrix.

Answer 4

It is made up of mainly type 1 collagen.

It gives the bone both flexibility and tensile strength (the ability to resist stretching).

Question 5

Describe the bone mineral.

Answer 5

It is mainly hydroxy apatite, which is hydrated calcium and phosphate (Ca10(PO4)6(OH)2).
It makes the bone rigid, brittle and gives it a high compressive strength (the ability to resist shortening).

Question 6

List the types of bone cells (and their origination).

Answer 6

The three main types of bone cells are:

• osteoblasts
• osteoclasts
• osteocytes

Mesenchymal (stromal) stem cells give rise to osteoblasts and osteocytes.
Haematopoietic stem cells give rise to all blood cells, and osteoclasts (which are the same lineage as macrophages).

Question 7

Describe osteoblasts.

Answer 7

• they are the bone forming cells
• they are derived from mesenchymal stem cells
• they secrete osteoid, the collagen matrix of bone
• they promote mineralisation of osteoid

Question 8

Describe osteoclasts.

Answer 8

• they are bone (digesting/) reabsorbing cells
• they derive from haematopoietic stem cells
• they are large and multinucleate
• they secrete acid to dissolve bone mineral and enzymes to digest the organic matrix
• their life cycle is controlled by apoptosis

Question 9

Describe osteocytes.

Answer 9

• they are terminally differentiated osteoblasts
• they’re encased in bone mineral matrix (lacunae)
• they extend multiple dendrites via minute canals in the bone matrix (canaliculi)
• the Lacunocanalicular system maintains communication between the bone surface and blood vessels
• they’re thought to coordinate osteoblast and osteoclast activity

Question 10

Describe bone remodelling in cortical bone.

Answer 10

Typically, there will be a leading edge where cells differentiate into osteoclasts and start digesting the bone. Behind that, there is osteoblast differentiation that will lay down new bone.
Thus, you have an advancing line of bone reabsorption and formation, which also leaves behind a ‘cement line’ that can be detected histologically.

Question 11

Describe bone remodelling in trabecular bone.

Answer 11

Along the surface of the trabecular struts, there will be an osteoclast eating away at the bone, then osteoblasts subsequently forming new bone.
There are also lining cells on the surface of the bone that detach underneath this, forming a basic multicellular unit.

Question 12

Describe the stages of bone remodelling.

Answer 12

1. ACTIVATION: the promotion of differentiation of new osteoclasts
2. RESORPTION: the duration of osteoclast activity, removing bones and creating pits
3. REVERSAL: the process by which you get osteoclast apoptosis, terminating its activity
4. FORMATION: osteoblast differentiation; formation of new osteoblasts which line the bone surface, forming new osteoid (new bone which subsequently becomes mineralised)

Question 13

What are some ways in which we can control bone remodelling?

Answer 13

• load-bearing exercises
• cytokines and other local signals
• endocrine:
  
  • oestrogen: inhibits osteocyte apoptosis, promotes osteoclast apoptosis (oestrogen is essential for skeletal health)
  • androgens

Question 14

Describe the induction of osteoclast differentiation by RANK ligand.

Answer 14

RANK (receptor activator of nuclear factor κ-B): a surface receptor on pre-osteoclasts, stimulates osteoclast differentiation.

RANK-ligand: produced by pre-osteoblasts and osteocytes; binds to RANK and stimulates osteocyte differentiation.

OPG (osteoprotegerin): decoy receptor produced by osteocytes; binds to RANK-L, preventing activation of RANK

Question 15

Describe the Wnt signalling pathway (as much as we need to know).

Answer 15

Wnt is a gene family that encodes for Wnt proteins, which are involved in developmental signalling throughout the animal kingdom. Thus, they are highly conserved genes.

It is a complex signalling pathway that is required for osteoblast differentiation.
It is negatively regulated by DKK (dickkopf) and sclerostin (SOST).

Question 16

What are some diseases of the bone?

Answer 16

RARE: mutations that affect key signals (they’re very rare, but have elucidated mechanisms)

LESS RARE: osteomalacia
the failure of bone mineralisation, so it goes soft, like cartilage

COMMON: osteoporosis
the thinning of bone associated with age, and is more common in women than men (because of the dramatic drop of oestrogen following menopause)

Question 17

List some bone diseases caused by mutation.

Answer 17

• Osteoporosis pseudoglioma
  the inactivation of LRP-5, the Wnt co-receptor
• Sclerosteosis and van Buchem disease
  mutation of the SOSt gene, inactivating the sclerotin protein -> excessive bone formation
• Osteopetrosis:
  a mutation inactivates the RANK-L protein

Question 18

What happens during osteoporosis?

Answer 18

• increase in bone resorption over formation
• loss of bone density
• increased fracture risk