W7L1 Bones Flashcards
What are the 2 types of bones, based on their structure?
- 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)
What is the structural and functional unit of cortical bone?
Osteon
What 3 types of proteins can osteoblast cells produce?
Structure proteins, regulatory proteins, and catabolic enzymes
What important structural proteins are produced by osteoblasts? (4 things)
- Type I Collagen (90% of proteins produced)
- Osteocalcin
- Osteonectin: both this and osteocalcin bind Ca2+ and hydroxyapatite
- Alkaline Phosphatase: mobilizes phosphate groups, important in formation of bone matrix
What two catabolic enzymes are produced by osteoblasts?
Collagenases, gelatenases
What is the most important function of osteoblasts?
Separation of bone tissue from the rest of the environment
What are the two phases of bone formation?
- Formation of osteoid
2. Mineralization
What is osteoid? How is it formed?
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
What is the major component of mineralization?
Hydroxyapatite: Ca5(PO4)3 OH
What happens when osteoblasts are enclosed/trapped in the bone tissue?
They become osteocytes. Also, their regulatory proteins / catabolic enzymes will be trapped, to have a later role
What cells trigger the resorption of bones?
Where do they originate from?
What do they need for differentiation + activation?
Osteoclasts
Originate from a hemopoietic cell line
Need M-CSF, RANK ligand, IL-6 to differentiate & activate
What do osteoclasts become once they attach to bone? What space do they form?
They become polarized cells, forming a resorption cavity
What 2 things do osteoclasts secrete into the resorption cavity?
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)
What is the effect of osteoclast secretion itno the resorption cavity?
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
Osteoclasts have receptors for what hormone? What does it do?
Calcitonin (from thyroid C cells)
Inhibits osteoclasts directly
What happens as a result of increased weight load on a bone, as in the case of starting a new exercise?
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.
When does remodeling occur?
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.
What is the mechanism for remodeling?
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.
How long does it take all our bone to be completely remodeled?
5-10 years
Faster with trabecular bones
What bone-related cells are affected by PTH and calcitriol?
Osteoblasts only (osteoclasts do not have receptors for these, but do have receptors for calcitonin)
What is the mechanism for how RANK ligand works?
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
What compound can osteoblasts produce to inhibit osteoclasts?
OPG: Osteoprotegerin
This binds to RANK ligand, preventing it from binding to RANK receptor
What happens if the ratio of RANK ligand to OPG is increased?
RANKL/OPG increase -> osteoclast activity increased
and vice versa if ratio is decreased
Glucocorticoids have what effect on bone-related cells?
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
What are the effects of estrogens on bone-related cells?
The RANK ligand / OPG ratio is decreased, thus protecting from osteoporosis
What are the effects of inflammation and tumor cells on osteoblasts?
Produce lots of cytokines which are similar to RANK ligand, thus can lead to activation of osteoclasts and resorption of bones
