9: Intro to Bone

Question 1

Osteoblasts are derived from:

Answer 1

mesenchymal stem cells, which also give rise to

fibroblasts, chondrobasts/cytes, and adipocytes.

Question 2

Function of Osteoblasts

Answer 2

Their function is to synthesize the
organic components of the bone matrix. Mineralization appears to be a passive process that does not require cellular activity once mature matrix is present.

Question 3

Osteoblast are commited to their lineage via expression of which to TFs

Answer 3

RUNX2 (Cbfa1) and osterix (SP7).

Question 4

In the Alizarin red/alcian blue prep… what do we expect to see if the RUNX2 is missing

Answer 4

all blue.. no formation of bone
cartilage = blue
calcified stuff = red

Question 5

Osteoblasts have two fates:

Answer 5

osteoblasts either undergo apoptosis or are embedded within newly secreted
matrix, and undergo terminal differentiation to osteocytes.

Question 6

Cells in bones responsible for mechanotransduction in bone.

Answer 6

Osteocytes
Important mechanotransductive
functions rely on the primary cilium, and mechanotransduction at the tissue level
depends on intercellular communications via gap junctions.

Question 7

Helpful stains for osteocytes

Answer 7

dental matrix protein 1 (DMP1) and sclerostin

(SOST) are useful histochemical stains for osteocytes.

Question 8

origin of Osteoclasts (what are they structually related to?)

Answer 8

Osteoclasts are of hematopoietic origin and are closely related to macrophages in
lineage, structure, and function.

Question 9

Terminal differentiation of osteoclasts requires

combinatorial signaling of both

Answer 9

M-CSF and RANKL

Question 10

What makes RANK ligand?

Answer 10

osteoblasts.

Question 11

What does osteoblasts make as a soluble decoy receptor for RANKL?

Answer 11

osteoprotegerin (OPG),

RANKL that binds to OPG is not able to bind RANK, and so high OPG levels inhibit terminal osteoclast differentiation.

Question 12

What stimulates osteoclast activity

Answer 12

PTH and 1, 25 di-OH-D

Question 13

What inhibits osteoclast activity

Answer 13

CAlcitonin

Question 14

multinucleated giant cells that bind tightly to the bone surface via
the sealing zone to enclose a compartment in which bone matrix can be degraded.

Answer 14

Osteoclasts

Question 15

multinucleated giant cells that bind tightly to the bone surface via the sealing zone to enclose a compartment in which bone matrix can be degraded.

Answer 15

Mature osteoclasts

Question 16

What two things do osteoclasts secreate to

1. Degrade mineral
2. Degrade bony matrix

Answer 16

Within this compartment, osteoclasts secrete HCl to dissolve the mineral and cathepsin
K to degrade the bone matrix proteins.

Question 17

STain to see osteoclasts

Answer 17

tartrate resistant acid phosphatase (TRAP)

Question 18

makes up ~80-85% of the total bone. Its function is primarily structural, providing protection for organs and levers used for movement.

Answer 18

Cortical bone

Question 19

Organization of Cortical Bone

Answer 19

osteons (also called Haversian systems), cylindrical structures in which concentric layers of bone matrix form lamellae around a central canal.

Question 20

What about cortical bone lends its resistance to fracture

Answer 20

The lamellar organization of osteons

Question 21

_____ of cortical bone is calficied

Answer 21

80-90%

Question 22

What part of bone is always on outside of bone and surrounds trabecular bone?

Answer 22

Cortical Bone

Question 23

What % of trabecular bone is calcified

Answer 23

15-25

Question 24

Function of trabecular bone

Answer 24

metabolic

Question 25

Accounts for most of the bone surface area and most of the remodeling activity. The large surface area is necessary to allow for mineral homeostasis.

Answer 25

Trabecular bone

Question 26

How is trabecular organization similar and different from cortical bone?

Answer 26

trabecular bone is normally organized in a lamellar fashion, but the individual trabeculae are too small to contain osteons.

Question 27

When do osteocytes make sclerosin and why

Answer 27

Make is when bone is mechanically loaded... goes to osteoblast to inhibit maturation. When mechanical loading is gone, remove repression

Question 28

formed by formation of osteoblasts from mesenchymal stem cells present within what will become the periosteum.

Answer 28

Intramembranous bone

Question 29

What bones are intramembranous

Answer 29

Examples of bones that are intramembranous in origin include many bones of the skull and the ribs.

Question 30

What type of bone is formed at the bone collar of a healing frx. ?

Answer 30

Intramembranous bone

Question 31

How do long bones remodel to increase in diameter?

Answer 31

Via intramembranous bone at the periosteal surface of long bones

Question 32

bones replace previously formed cartilage models

Answer 32

Endochondral

Question 33

How do Endochondral bones grow?

Answer 33

grow in length by proliferation of chondrocytes within the growth plate, a specialized structure present within growing endochondral bones. Linear growth ceases when the growth plates fuse.

Question 34

Examples of endrochondral bones

Answer 34

the long bones of the limbs.

Question 35

highly organized tissue in which chondrocytes are arrayed in columns, with different positions within the column occupied by cells at a distinct point of maturation.

Answer 35

The growth plate

Question 36

How do chondrocytes grow during growth phase

Answer 36

is a Chondrocytes in the proliferative zone divide, replenishing the growth plate. The chondrocytes then hypertrophy, undergo apoptosis, and are mineralized. Blood vessels invade the zone of calcified cartilage, which is resorbed by chondroclasts and the space is filled by osteoblasts and bone matrix.

Question 37

Linear growth of the long bones | depends on

Answer 37

the relative speed with which cells in the hypertrophic zone undergo apoptosis and those in the proliferative zone divide.

Question 38

In humans, the growth plates close in late adolescence in response to

Answer 38

estrogen signaling.

Question 39

Which has more active remodeling: cortical or trabecular

Answer 39

At any given time, about 10% of the skeleton is being remodeled. Trabecular bone is much more actively remodeled than cortical bone. This makes sense in light of its more prominent role in maintaining mineral homeostasis.

Question 40

2 key principles in bone remodeling

Answer 40

First, bone resorption and bone formation are coupled processes. Second, bone resorption is relatively rapid, requiring ~2 weeks, while bone formation is slow, requiring 4-6 months for full mineralization to take place.

Question 41

Method of measuring bone remodel?

Answer 41

Tetracycline labeling

Question 42

Bone's role in moment-moment homeostasis

Answer 42

The amount of Ca exchanged by trabecular bone each day is approximately twice the amount that is absorbed from food or lost in urine each day. This active exchange of minerals between the bone and the circulation is essential for moment-to-moment mineral homeostasis.

Question 43

Bones do not only grow in length, but grow in radial size and change shape as well: this is called

Answer 43

``` Bone modeling (dt mechanical loading) ```

Question 44

At the level of the whole bone, ________is the primary stimulus to modeling

Answer 44

strain (fractional change in length)

Question 45

At the level of the cell, ________, requiring both anchoring of osteocytes by focal adhesion complexes and fluid flow sensed by each cell’s primary cilium appear to be the critical stimulus.

Answer 45

shear stress

Question 46

How do bones direct their growth at the appropriate site?

Answer 46

The connections among the osteocytes via their processes allow integration of the response across cells, allowing new bone growth to be directed to the sites experiencing the greatest strain.

Question 47

_____forms at the fracture site, which becomes organized as a consequence of the inflammatory process.

Answer 47

hematoma

Question 48

After hematoma formation... mesenchymal stem cells are present and become chondrocytes so they can:

Answer 48

form a cartilaginous soft callus.

Question 49

How does a hard callus form

Answer 49

Blood vessels invade the soft callus and bone replaces cartilage in a process very similar to that seen in the growth plate, forming a hard callus.

Question 50

Durning hard callus formation... what goes on with the osteoblasts

Answer 50

osteoblasts on the subperiosteal surface form an intramembranous bone collar.

Question 51

The hard callus is much bigger at first then what it ends up being... how does that happen

Answer 51

callus undergoes remodeling to form lamellar bone and modeling

Question 52

How long does it take to heal a fracture

Answer 52

Time required is ~8-12 weeks, though the final remodeling and mineralization may take considerably longer.

Question 53

bone, compressive strength comes from the

Answer 53

mineral phase (about 2/3 of the bone extracellular matrix by mass),

Question 54

Bone tensile strength comes from the

Answer 54

protein and water (about 1/3 of the bone extracellular matrix by mass).

Question 55

Primary protein compoment of bone's ECM

Answer 55

type 1 collagen. This is a large triple helical protein that self-assembles into fibrils with an offset of ~1/4 the molecule length, leading to a regular striped appearance on electron microscopy, with a periodicity of ~6.7 nM.

Question 56

Assembly of toropcollagen into fibers provides

Answer 56

tensile strength: more x-linking = stronger

Question 57

IN type I collagen: mature aromatic cross-links have higher bond energy than the aliphatic cross-links, thus:.

Answer 57

and are therefore harder to break

Question 58

Collagen: packs tight or loose forms covalent bonds, non-covalent bonds formation depends on which Vitamin

Answer 58

Tight covalent Vit C dependent

Question 59

______ structure of the individual collagen molecules allows them to be stretched, for tensile strength

Answer 59

Helical

Question 60

Cracks in bone have outcomes based on cement lines and toughness: Which cracks propagate ealisly

Answer 60

ones along longitudinal lines | Transverse cracks are less able to propagate

Question 61

Most abundant minerals in bone

Answer 61

Ca and PO4 are the most abundant ions in bone mineral, but significant amounts of Mg, Na, OH, CO3, SO4, and Cl are also present

Question 62

Disease of OsteoBlasts resulting in bones that easily frx

Answer 62

Osteogenesis Imperfecta

Question 63

What is the pathology of osteogeneis imperfecta

Answer 63

Type I col defect, either synthesis or assembly. See bent fibrils, see bowing of legs

Question 64

inadequate mineralization of the bone matrix and can be a consequence of several different conditions, including various malabsorptive disorders, vitamin D deficiency or resistance, phosphate wasting disorders, or even low Ca diet.

Answer 64

Cause Osteomalacia

Question 65

Osteomalacia causes what type of bones

Answer 65

weak, undermineralized bones

Question 66

What happens in growing individual gets osteomalacia

Answer 66

bone modeling is abnormal and the long bones assume a bowed shape. This is called rickets. --not dt abnormal cellular funx but lack of appropriate substrates

Question 67

disorders in which the skeletal mass is | abnormally high, due to mutations of the protein sclerostin.

Answer 67

Sclerosteosis and Van Buchem’s disease

Question 68

Pathology of Sclerosteosis

Answer 68

Lack of sclerostin the mechanosensory system, resulting in bones perceiving that they are being loaded even when they are not. These can be thought of as osteocyte diseases.

Question 69

group of diseases in which osteoclast function or maturation is impaired. As a result, remodeling is deficient.

Answer 69

Osteopetrosis

Question 70

disorder characterized by focally excessive and | disorganized bone remodeling.

Answer 70

Pagets

Question 71

see presenence of woven bone and increased serum alkaline phosphatase and urinarly hydroporline increase

Answer 71

Pagets

Question 72

Pagets increases disposition to

Answer 72

osteosarcoma