Muscle And Integument: Bone Remodeling

Front 1

T/F: Bone is a dynamic living material, constantly being renewed and reconstructed throughout life.

Back 1

T.

Front 2

Give three ways to increase serum calcium levels.

Back 2

1) release of calcium from matrix: PTH
2) retention of calcium by kidney: PTH
3) absorption of calcium by gut: PTH -> calcitriol

Front 3

Majority of calcium is excreted in ___ whereas majority of phosphate is excreted in ___.

Back 3

Majority of calcium is excreted in feces whereas majority of phosphate is excreted in urine.

Front 4

Name the hormone:

- promote Ca2+ absorption in the gut
- secreted by kidney
- stimulated by PTH

Back 4

calcitriol

Front 5

Name the hormone:

- stimulate bone resorption
- act on kidney to decrease loss of Ca2+ in the urine
- stimulate kidney to form calcitriol which promote Ca2+ absorption in the gut

Back 5

PTH

Front 6

What is this process called?

- osteoclasts first carve out small tunnels in old bone tissue
- then osteoblasts rebuild it

Back 6

remodeling

Front 7

What are the 2 purposes of remodeling?

Back 7

1) renew bone tissue before deterioration
2) redistribute bone matrix along lines of meechanical stress

Front 8

Injured bone heals by which process?

Back 8

remodeling

Front 9

Modeling or remodeling?

- bone resorption in some places and bone formation in others with independent actions of osteoclasts and osteoblasts

Back 9

modeling

Front 10

Modeling or remodeling?

- removal and replacement of bone in particular places by coupled actions of osteoclasts and osteoblasts working at the same site.

Back 10

remodeling

Front 11

Modeling or remodeling?

- results in change of bone size

Back 11

modeling

Front 12

Modeling or remodeling?

- does not results in change of bone size

Back 12

remodeling

Front 13

Modeling or remodeling?

- process stops after skeletal maturity, usually in the 20s.

Back 13

modeling

Front 14

Modeling or remodeling?

- process continues throughout life

Back 14

remodeling

Front 15

Modeling or remodeling?

- process is prolonged and continuous

Back 15

modeling

Front 16

Modeling or remodeling?

- process is episodic

Back 16

remodeling

Front 17

What is BMU?

Back 17

Basic multicellular unit:
- consist of 10 osteoclasts and hundreds of osteoblasts
- 1-2 million sites per skeleton

Front 18

Bone resorption takes about ___ per site whereas rebuilding takes about ___.

Back 18

Bone resorption takes about 3 wks per site whereas rebuilding takes about 3-4 months.

Front 19

Which period of life is this and what process is involved?

- bone formation > resorption
- linear increase skeletal mass

Back 19

Growth period: 0-20 yrs
modeling

Front 20

Which period of life is this and what process is involved?

- bone formation = resorption
- maintained peak bone mass
- influenced by mechanical usage

Back 20

young adult till age 30-40: remodeling

* exercise very important

Front 21

Which period of life is this and what process is involved?

- bone formation < resorption
- decrease in skeletal mass

Back 21

Senescence: begins at about age 35

Front 22

What is the typical frature threshold of bone mass (grams of calcium)?

Back 22

500

Front 23

Organic portion of bone matrix is made by which cell?

Back 23

osteoblasts: make osteoid
- type I collagen
- osteocalcin: binds to hydroxyapatite, attract bone cells
- glycoproteins: osteonectin, osteopontin and sialoprotein(RGD sequence, binds osteoclasts integrins to bone surface)
- proteoglycans: chondroitin sulfate, may bind TGF-beta.

Front 24

What is the content of osteoid?

Back 24

- type I collagen
- osteocalcin: binds to hydroxyapatite, attract bone cells
- glucoproteins: osteonectin, osteopontin and sialoprotein(RGD sequence, binds osteoclasts integrins to bone surface)
- proteoglycans: chondroitin sulfate, may bind TGF-beta.

Front 25

What is a reliable serum marker for bone formation?

Back 25

osteocalcin: directly related to osteoblast activity.

Front 26

How does osteoblast regulate energy metabolism?

Back 26

starvation -> adypocyte -> leptin -> osteocalcin(osteoblast) -> pancreatic beta cell -> insulin release

Front 27

Which type of protein is osteocalcin?

Back 27

Gla protein: calcium binders

* but osteocalcin does not bind calcium.

Front 28

Which vitamine regulate osteocalcin expression in osteoblasts?

Back 28

Vit D3 (calcitriol): stimulate expression of RANKL

Front 29

Name the two osteoblast specific genes.

Back 29

- Cbfa1: key factor controlling the expression of multiple genes required to make bone matrix.
- osteocalcin

Front 30

Which growth factors control the differentiation of osteoblasts?

Back 30

- BMP
- FGF
- PDGF
- IGF
- TGF-beta

Front 31

Which growth factor is this?

- induce mesenchymal tissue into bone
- induce endochondrial ossification
- regulate ECM production

Back 31

BMP

Front 32

Which growth factor is this?

- stimulate proliferation of osteoblasts and chondroblasts
- stimulate angiogenesis

Back 32

FGF

Front 33

Which growth factor is this?

- stimulate proliferation of osteoblasts to increase collagen synthesis

Back 33

PDGF

Front 34

Which growth factor is this?

- stimulate bone resorption by increasing the number of osteoclasts

Back 34

PDGF-BB

Front 35

Which growth factor is this?

- stimulate proliferation of osteoblasts
- stimulate bone collagen and matrix synthesis
- inhibit collagen degradation

Back 35

IGF

Front 36

Which growth factor is this?

- promote proliferation and differentiation of mesencymal precursor for osteoblasts, osteoclasts, and chondrocytes.
- stimulate both endochondral and intramembranous ossification.

Back 36

TGF-beta

Front 37

Describe the central relay mechanism of leptin.

Back 37

Adipocyte -> leptin -> hypothalamus -> inhibit bone formation

Front 38

Describe the bone in people with generalized lipodystrophy.

Back 38

accelerated bone growth: lack of leptin

Front 39

Growth factors BMP, IGF, FGF, PDGF, TGF-beta are secreted by which cells in the bone?

Back 39

osteoblasts

Front 40

Mineralization of bone matrix (osteoid) by osteroblasts is mediated by ___.

Back 40

matrix vesicles: enriched in alkaline phosphatase

Front 41

Which three secretory products of osteoblasts are required for regulating the differentiation of osteoclasts?

Back 41

- M-CSF: stimulate macrophage to express RANK
- RANKL: bind to RANK on pre-osteoclast
- osteoprotegerin (OPG): in absence of PTH, it competes with RANK for RANKL

Front 42

How long is the mineralization lag time?

Back 42

10 days

Front 43

Mineralization depends on which molecules?

Back 43

- plasma ca2+, phosphate
- calcitriol
- alkaline phosphate

Front 44

Are there gap junctions between osteoblasts?

Back 44

Yes. They are formed in groups of up to 400 cells and communicate through gap junctions.

Front 45

Describe the stages of osteoclast differentiation.

Back 45

- monocyte
- macrophage: express RANK in response to M-CSF
- pre-osteoclast: RANK bind with RANKL on osteroblast
- resting osteoclast
- functional osteoclast: has integrin which attach to osteopontin.

Front 46

What are the effects of PTH on osteoblasts?

Back 46

- stimulate production of M-CSF
- stimulate synthesis of RANKL
- blocks synthesis of OPG

Front 47

Name two molecules that stimulate M-CSF expression on bone stromal cells.

Back 47

- TNF
- IL1

Front 48

What is the effects of estrogen?

Back 48

Inhibit bone resorption: inhibit effects of IL1 and TNF

Front 49

Osteoclasts activities are regulated by ____.

Back 49

calcitonin and regulatory molecules produced by osteoblast/stromal cells of the bone marrow.

Front 50

Describe the process of bone resorption by osteoclasts.

Back 50

1) attachment to bone surface: sealing zone
- osteopontin
- sialoprotein

2) carbonic anhydrase procude H+ and HCO3-.

3) H+ pump and Cl channel acidify Howships lacuna to pH4.5: dissolve calcium phosphate crystals

4) cathepsin K digest collagens and other matrix components. acid phosphatases acivated by acidic environment.

Front 51

Name a non-lysosomal enzyme in osteoclasts.

Back 51

cathepsin K
metallo proteinases

Front 52

Name a lysosomal enzyme in osteoclasts.

Back 52

cysteine-proteases
phosphatases

Front 53

Describe the 6 phases in compact bone remodeling.

Back 53

1) activation: 3 days
- osteoclasts

2) resorption: activated osteoclasts
- cutting cone: 40uM/day

3) reversal: 30 days (resorption + reversal)
- transition form osteoclast to osteoblast activity

4) formation: 3 months, 1-2uM/day
- osteoblasts lay concentric lamellae
- need vascular loop
- form Haversian canal

5) mineralization: 10 days lag time
- primary: first few days
- seconday: decreasing rate for 6 months

6) resting:
- osteoclasts disappear
- osteoblasts become osteocytes

Front 54

Cement line is the same as ___ line.

Back 54

reversal line

Front 55

Which line marks the reversal zone during bone remodeling process?

Back 55

cement line

Front 56

How is remodeling of cancellous bone different from compact bone?

Back 56

- high rate
- BMUs work on trabecular suface

Front 57

Does remodeling occur on endosteal and periosteal surface?

Back 57

Yes. Responsible for radial expansion of long bones in children and adults.

Front 58

Packet of new bone produced by BMU is called ____.

Back 58

bone structural unit.

Front 59

Which is the most abundant of all growth regulatory factor in bone?

Back 59

TGF-beta

Front 60

What is the role of TGF-beta in bone remodeling?

Back 60

1) activation of osteoblast:
- deposit new bone
- increase capacity of unidirectional migration

2) inhibit osteoclast formation and bone resorption

Front 61

Which of the following TGF-beta is targeted for storage in bone?

- 100kD latent TGF-beta
- 290kD latent TGF-beta

Back 61

290kD latent TGF-beta

Front 62

What is the role of latent TGF-beta stored in the bone?

Back 62

osteoclasts activity -> acid environment -> activate 290kD latent TGF-beta -> activate osteoblasts -> proliferation osteoblatss -> 100kD latent TGF-beta (easily activated, circulating) -> more differentiated osteoblasts -> 290kD TGF-beta -> stored in bone

Front 63

What are the two ways osteonal remodeling replaces microdamage?

Back 63

1) directing BMU to the site of damage

2) random remodeling cortex at a rate designed to keep up with overall rate of damage accumulation (not ideal)