Bones

Question 1

What is the extracellular matric of bone made of?

Answer 1

Made of calcified material and Collagen type I
Clacification = build up of Calcium

Question 2

What are the cell types present in bones?

Answer 2

• Osteoprogenitor cells → stem cells derived from mesenchymal cells
• Osteoblasts → derived from osteoprogenitors, synthesize the organic components of ECM
• Osteocytes → dervied from osteoblasts, found in lacunae
• Osteoclasts → derived from osteoprogenitor cells, big round multinucleated cell, involved in bone resorption (remodelling) to provide Ca to the blood

Question 3

Why are osteoclasts multinucleated?

Answer 3

They need to produce lots of enzymes to breakdown bone
- To do so, need lots of DNA for quick transcription

Question 4

What is the ground substance of the bones?

Answer 4

Proteoglycans
Glycoproteins → sialoprotein, osteocalcin

Question 5

What minerals are found in the ECM of bones?

Answer 5

Crystals of hydroxyapatite → Ca10(PO4)6(OH)2)
*Lots of Ca in bones

Question 6

How can bones be prepared for microscopic visualisation?

Answer 6

Requires special technique because glass blade would break
Special technique = decalcification → 5% nitric acid or EDTA treatement (takes Ca out of the bones)
*Gives rubber material

Question 7

What are the 3 ways of classifying/defining bone?

Answer 7

1. Gross Appearance:
   - compact
   - cancellous (spongy)
2. Microscopy Appears
   - woven (immature) → spongy bone
   - lamellar (mature) → compact bone
3. Development Appear
   - intramembranous → within a membrane, sheath of mesenchymal cells become a sheath of bone → sheaths fuse together eventually (flat bones → ex: skull)
   - endochondral → formed from pieces of cartilage

Question 8

What are the parts/structure of compact bone?

Answer 8

outside → inside (bone marrow):
1. Periosteum → Fibrocytes + Osteoprogenitors
2. Outer circumferential system → parallele to periosteum, osteocytes struck in bone ECM
3. Haversian system + Interstitial system
4. Inner circumferential system → parallel to endosteum, layer of osteocytes
5. Endosteum → hard to see because 1 layer of very flat cells, closest to bone marrow, osteoprogenitor cells + osteoblasts

Question 9

What shape do osteocytes appear to have? why?

Answer 9

Have spider-like projection called cellular processes that connect osteocytes between each other and connect to Volkmann’s canals to have access to nutrients and reject organic wastes
(though gap junctions)

Question 10

What is a Haversian system? What are its characteristics and roles?

Answer 10

Haversian lamellae = Haversian system
Also called Osteon
- Perpendicular to periosteum
- Lengthwise with the bones
- Different haversian systems are connected by Volkmann’s canals
- Nerves and blood vessels run through Haversian canal in the middle of each Haversian system
- Composed of osteoblasts (at surface of haversian canal) and osteocytes

Question 11

What is Volkmann’s canal?

Answer 11

They connect Haversian systems
- Run perpendicular to muscles
- Have blood vessels, nerves, lymphatic vessels

Question 12

Describe the Priosteum as a layer?

Answer 12

Connective tissue sheath surrounding a compact the bone

Outer fibrous layer: (dense CT)
Made of collagen, elastin, and fibroblasts, this layer provides structural integrity and contains most of the periosteum’s blood vessels and nerves.
Inner osteogenic layer:
Contains osteoprogenitor cells, which develop into osteoblasts that create new bone. This layer is also responsible for bone repair and remodeling.

Question 13

What is the structure/the components of Trabecular bones?

Answer 13

*Trabecular bones = spongy bones
- Surrounded by osteoblasts (on the outside making the ECM)
- Osteoclasts are also found on the outside (almost only seen in trabecular, not in compact)
- Osteocytes trapped inside the ECM
- found at the epiphysis of the long bones

Question 14

What are interstitial systems?

Answer 14

• Not circle
• Old haversian systems degrading and turning over

Question 15

What is the orientation of the type 1 collagen in the bones?

Answer 15

→ Forms alpha helices lengthwise with the muscle
Gives strength to the muscle

Question 16

What is the cementing line?

Answer 16

It divides 2 neighbour haversian systems → each haversian system is isolated

Question 17

What is different in a developping osteon (haversian system) than in a mature one?

Answer 17

Just outside the osteoblasts layer/endosteum, pre-bone stains light pink (no osteocytes trapped in matrix, matrix is getting calcified)
REVIEW

Question 18

How do osteoclasts act in bones?

Answer 18

1. Osteoclasts hang around waiting for signal
2. When low Ca in the blood → body stops making bone → signal sent to osteoclasts??????????
3. Osteoclasts sits on bone matrix
4. Carbonic anydrase promotes synthesis of H+ (from CO2 + H2O → H+ + HCO3-)
5. Osteoclast pumps HCO3- to the blood capillary and H+ to the bone matrix surface making an acidic microenvrionment
6. Acidic phosphatase (translated in the Golgi) is packaged into lysosomes and brought to the ruffled border of the acidic microenvrionment
   → Acidic phosphatase only works in acidic envrionment and breaks down bones (Tartrate-resistant acidic phosphatase/TRAP)
7. Ca from the bone breakdown is then sent through the osteoclast to the blood vessel
8. When Ca levels are restored, osteoclast gets the signal to stop

Question 19

What area of the long bone has periosteum?

Answer 19

*At the diaphysis
All where there was hyalin cartilage that was surrounded by perichondrium (which becomes the periosteum)
At both ends, there was articular cartilage (no perichondrium) → no periosteum

Question 20

What bones develop by intramembranous ossification?

Answer 20

Flat bones → part of mandible, maxilla, occipital, temporal and parietal bones

*Not for long bones
*Generally spongy bone

Question 21

What is the process of intramembranous ossification?

Answer 21

Takes place within plates of mesenchymal cells
1. Primary ossification center
2. Synthesisi of ECM
3. Encapsulation of ostocytes, formation of spicules, Osteoblasts are surrounding the primary bone tissue
4. Secondary ossification centers develop in parallel + on the periphery, mesenchymal cells differentiate into periosteum
5. Ossification centers grow radially and fuse → bone (generally spongy)
6. Lamellar bone formation → as the spongy bone develops, it may be remodeled into lamellar bone, more organized and dense

Question 22

What bones develop by Endochondral Ossification?
What are the names of the main general steps?

Answer 22

Long bones
Takes place within a piece of hyalin cartilage with similar shape of the bone to be formed. The cartilage is surrounded by perichondrium except in the furture articular surfaces.

1. Primary Ossification center
2. Sencondary Ossification centers
3. Remodeling

Question 23

What happens in the Primary ossification center formation of Endochondral Ossification?

Answer 23

1. At the levels of the diaphysis, the perichondrium → bone collar (periosteum)
2. The bone collar prevents diffusion of nutrients → cartilage degenerates (hypertrophy and cell death followed by calcification of ECM)
3. Blood vessels invade form the perichondrium/periosteum the space left by degenerating chondryctes and carry oseoprogenitor cells
   *This will become the epiphyseal plate
4. Differentiating oseoblstats divide and secrete ECM

Question 24

What happens in the Primary and the Secondary ossification centers formation of Endochondral Ossification?

Answer 24

Primary = diaphysis of the future bone
Secondary = both epiphysis
2. Same as process as primary ossification center, but caritlage persists in articular surface (no perichondrium/periosteum to cut nutrients)
- Epiphyseal plate separates primary from secondary on both sides

*2 epiphyseal plates at both ends of the long bones

Question 25

What is the remodeling step of Endochondral ossification?

Answer 25

Osteoclasts are active in the resorption of calcified cartilage and woven bone → formation of hollow marrow *Chew up calcified cartilage and spicules (pieces of bone)

Question 26

What are the layers from the epiphyseal plate? What cells are found in each layer?

Answer 26

1. Zone of resting cartilage → Chondrocytes in lacunas 2. Zone of proliferation → Chondrocytes dividing (no isogenic group bc each take up their own lacuna) 3. Zone of hypertrophy → Lacuna filling with fluid so chondrocytes swell 4. Zone of cell death → dead chondrocytes 5. Zone of mixed spicules → calcified cartilage (no cells), osteoblasts (no in matrix), osteocytes (in matrix), osteoclasts (multinucleated)

Question 27

What specific proliferation allows growth in length of the long bones?

Answer 27

Proliferation of chondrocytes in the epiphyseal plate Rate of chondrocyte proliferation and bone formation = destruction of spicules → thickness of epiphyseal plate does not change, instead is displaced away from the middle of the diaphysis → Both epiphyseal plates get farther from each other

Question 28

What type of bone are spicules formed by?

Answer 28

Spicules are formed by woven bone, NOT lamellar bone

Question 29

What are the 5 shaping (partial remodeling) mechanisms associated with bone growth?

Answer 29

1. Growth in length → chondrogenesis 2. Radial growth → perichondrium 3. Formation of new spicules by lateral invasion of blood vessels (bringing osteoprogenitors) 4. Remodeling of the funnel → periostal osteoclasts (head/outisde shape of the bone) 5. Addition of bone from osteoblasts on periostal surface → thickening + increased density

Question 30

What occurs in the bones in case of low [Ca]?

Answer 30

Parathyroid hormone (PTH) → osteoblasts to stop producing bone + start secreting Osteoclast Stimulating Factor → activates osteoclasts to chew up Ca in bones

Question 31

What occurs in the bones when the blood [Ca2+] level are restored?

Answer 31

Thyroid gland produce hormone calcitonin → inhibits bone resorption (tells oseoclasts to stop)

Question 32

What are 3 diseases that can be due to misregulation of the Growth Hormone?

Answer 32

Pituitary dwarfism → lack of GH → problem in epiphyseal plate Gigantism → youngsters with excess GH → epiphyseal plate keeps growing Acromegaly → adult with excess GH, periosteal growth (by tumous in PTH) → big hands and feet