W7L1 Bones

Question 1

What are the 2 types of bones, based on their structure?

Answer 1

1. Cortical bone (dense, describes 80% of bones)

2. Trabecular bone (20% of bones, found in vertebral bodies, has high surface area for bone formation/resorption)

Question 2

What is the structural and functional unit of cortical bone?

Answer 2

Osteon

Question 3

What 3 types of proteins can osteoblast cells produce?

Answer 3

Structure proteins, regulatory proteins, and catabolic enzymes

Question 4

What important structural proteins are produced by osteoblasts? (4 things)

Answer 4

1. Type I Collagen (90% of proteins produced)
2. Osteocalcin
3. Osteonectin: both this and osteocalcin bind Ca2+ and hydroxyapatite
4. Alkaline Phosphatase: mobilizes phosphate groups, important in formation of bone matrix

Question 5

What two catabolic enzymes are produced by osteoblasts?

Answer 5

Collagenases, gelatenases

Question 6

What is the most important function of osteoblasts?

Answer 6

Separation of bone tissue from the rest of the environment

Question 7

What are the two phases of bone formation?

Answer 7

1. Formation of osteoid

2. Mineralization

Question 8

What is osteoid? How is it formed?

Answer 8

Osteoid = protein matrix of bones, gives elasticity and (importantly) site for nucleation of hydroxyapatite

Collagen is secreted (initially as monomers, then forms fibers), calcium plays an important role in cross-linking. Takes about 2 weeks to mature, then have strong and dense protein matrix

Question 9

What is the major component of mineralization?

Answer 9

Hydroxyapatite: Ca5(PO4)3 OH

Question 10

What happens when osteoblasts are enclosed/trapped in the bone tissue?

Answer 10

They become osteocytes. Also, their regulatory proteins / catabolic enzymes will be trapped, to have a later role

Question 11

What cells trigger the resorption of bones?

Where do they originate from?

What do they need for differentiation + activation?

Answer 11

Osteoclasts

Originate from a hemopoietic cell line

Need M-CSF, RANK ligand, IL-6 to differentiate & activate

Question 12

What do osteoclasts become once they attach to bone? What space do they form?

Answer 12

They become polarized cells, forming a resorption cavity

Question 13

What 2 things do osteoclasts secrete into the resorption cavity?

Answer 13

Protons and TRAP (Tartrate-Resistant Acid Phosphatase, but you just need to know the acid phosphatase part)

(schematic was drawn during lecture, should review it)

Question 14

What is the effect of osteoclast secretion itno the resorption cavity?

Answer 14

The protein content (osteoid) is degraded

Also the regulatory proteins and catabolic enzymes that were produced by osteoblasts & stored in the bone are released. These further activate osteoclast cells

Question 15

Osteoclasts have receptors for what hormone? What does it do?

Answer 15

Calcitonin (from thyroid C cells)

Inhibits osteoclasts directly

Question 16

What happens as a result of increased weight load on a bone, as in the case of starting a new exercise?

Answer 16

The bone adapts via modeling. Resorption occurs, then new bone is formed to be stronger.

Fluid movement in the bone canaliculi is changed by mechanical stimuli, which is sensed by osteocytes, activating osteoblasts, which activate osteoclasts to resorb bone tissue.

Question 17

When does remodeling occur?

Answer 17

When there is no change of load, but under completely normal constitutive activity. This is balanced, unless the calcium and phosphate concentrations are not normal.

Question 18

What is the mechanism for remodeling?

Answer 18

Initiated by osteoclast cells (don’t need activation of osteocytes), which resorb bone matrix and produce resorption tunnel. Then there will be activation of osteoblasts to form new bone, but it’ll be exactly the same as the old bone.

Question 19

How long does it take all our bone to be completely remodeled?

Answer 19

5-10 years

Faster with trabecular bones

Question 20

What bone-related cells are affected by PTH and calcitriol?

Answer 20

Osteoblasts only (osteoclasts do not have receptors for these, but do have receptors for calcitonin)

Question 21

What is the mechanism for how RANK ligand works?

Answer 21

In response to PTH and calcitriol, osteoblasts produce RANK (Receptor for Activation of Nuclear Factor Kappa B) ligand, which binds to RANK receptor in osteoclast membrane, causing osteoclast activation

• > resorption
• > calcium and phosphate mobilization

Question 22

What compound can osteoblasts produce to inhibit osteoclasts?

Answer 22

OPG: Osteoprotegerin

This binds to RANK ligand, preventing it from binding to RANK receptor

Question 23

What happens if the ratio of RANK ligand to OPG is increased?

Answer 23

RANKL/OPG increase -> osteoclast activity increased

and vice versa if ratio is decreased

Question 24

Glucocorticoids have what effect on bone-related cells?

Answer 24

Cause osteoblasts to increase RANK ligand / OPG ratio, thus activating osteoclasts -> resorption

These cause a huge stimulation, and this the reason why prolonged steroid treatment or Cushing’s syndrome -> osteoporosis

Question 25

What are the effects of estrogens on bone-related cells?

Answer 25

The RANK ligand / OPG ratio is decreased, thus protecting from osteoporosis

Question 26

What are the effects of inflammation and tumor cells on osteoblasts?

Answer 26

Produce lots of cytokines which are similar to RANK ligand, thus can lead to activation of osteoclasts and resorption of bones