Bone Handout

Question 1

What is aggrecan?

Answer 1

• Negatively charged proteoglycan monomer which attracts water molecules
• This allows for the resilience of cartilage.
• Multiple aggrecan molecules attach to Hyaluronic acid molecule to form an aggregate.
• Charged aggregates attach to collagen via electrostatics.

Question 2

Glycosaminoglycans + a core protein = ?

Answer 2

Proteoglycan monomer (aggrecan)

Question 3

Perichondrium

Answer 3

• Surrounds Hyaline and Elastic cartilage (except at articular surfaces).
• Provides blood supply to chondrocytes and therefore is responsible for maintenance and growth of cartilage. Nutrient exchange via compression and diffusion.
• Contains reserve cells
• Outer layer is fibrous with type I collagen and fibroblasts
• Inner layer contains chondroblasts

Note1: Fibrocartilage lacks Perichondrium.

Note2: Articular surfaces rely on synovium to provide nutrients since they lack perichondrium.

Question 4

Cartilage Growth

Answer 4

• Interstitial
• Appositional
• Interstitial growth occurs through mitosis of chondrocytes
• Appositional growth occurs through maturation of chondroblasts in inner perichondrium.

Question 5

Cartilage Repair

Answer 5

• Limited capacity due to avascular nature
• Scars if severely damaged

Clinical:

• Severe damage can result in Osteoarthritis
• Chondrocytes proliferate and release degrading enzymes and cytokines that destroy matrix.

Question 6

Vertical Bone Architecture (Top to bottom)

Answer 6

• Epiphysis
• Epiphyseal plate (Growth plate)*
• Metaphysis
• Diaphysis

Note: In adults the epiphyseal plate is identified as epiphyseal line.

Question 7

Histological Long Bone types

Answer 7

Woven = Immature bone
Compact= Outer portion of Mature bone
Spongy (aka Trabecular or Cancellous) = Inner portion of bone

-Woven bone has disorganized matrix.

Question 8

Periosteum

Answer 8

• Covers the outer surface of bones (except articular surfaces, and tendon/ligament insertions).
• Vascularized
• Contain osteoprogenitor cells.

Question 9

Endosteum

Answer 9

• Contain cells belonging to marrow stroma

- Source of cells that line Haversian canals.

Question 10

1) Name all the Bone Cells

2) All except one is derived from Undifferentiated Mesenchymal cells. Which one?

Answer 10

• Osteoprogenitor cells
• Osteocytes
• Osteoblasts
• Osteoclasts
• Lining cells

-Osteoclasts are of Hematopoetic lineage

Question 11

What are Osteoprogenitor Cells?

Answer 11

-Differentiate into Osteoblasts when stimulated by transcription factor.

Question 12

What are Osteoblasts?

Answer 12

• Responsible for laying down bone.
• Secrete type I collagen and Osteoid.

-Osteoid becomes calcified with Hydroxyapetite (source of calcium and phosphate).

Note: Contain receptors for Parathyroid Hormone.

Question 13

What are Lining cells?

Answer 13

Lining cells are Osteoblasts that have finished laying down Osteoid.

• Found in endosteum
• Found lining the Haversian (central) canals in compact bone and the spicules of spongy (or Trabecular/cancellous) bone.

Question 14

What are Osteocytes?

Answer 14

Osteocytes are Osteoblasts that have been completely surrounded by calcified matrix.

• Maintain the Matrix.
• Involved with Calcium Homeostasis.
• Found in Lacunae.
• Contain long cellular processes that extend into cannaliculi and allow them to communicate via Gap Junctions.

Question 15

Name the Different States of Osteocytes

Answer 15

• Quiescent
• Formative
• Resorptive

Note: Based on environmental conditions, osteocyte can synthesize and degrade.

Question 16

What are Osteons?

Answer 16

Highly organized structures that form Functional unit of bone.

• Long structures that run parallel to diaphysis of bone.
• Consists of a Central canal with blood vessels, nerve, and lining cells within it.
• Perforating vessel connects to Central Canal.
• Lacunae with Osteoblasts
• Resorptive channels with Osteoclasts

Question 17

Cancellous Bone

Answer 17

• Lack a central canal
• Blood supply from highly vascular marrow cavity.

-Osteoclasts are present on the outer surface of Trabeculae in Cancellous (aka Spongy or Trabecular bone).

Question 18

What are Osteoclasts and where do they come from?

Answer 18

• Multinucleated large cells of Hematopoetic lineage.
• Develop from a stem cell and the fusing of many monocytes.
• Contain RANK on their surface.
• Contain receptors for Calcitonin (but not for PTH).

-Involved with the breakdown, remodeling, and resorption of bone.

Question 19

Describe the Ruffled border of Osteoclasts

Answer 19

• Infoldings on the surface of Osteoclasts which create a microenvironment.
• Microenvironment is Acidic
• Site of Hydrolytic enzyme release
• Site of ATP-dependent Proton pump for H+ release.
• Site of endocytosis of debris from breakdown process

Clinical: Bisphosphonates induce Apoptosis in Osteoclasts and are used as Osteoporosis Rx.

Question 20

Type I Collagen

Answer 20

• Comprises 90% of bone matrix.

- Ground Substance makes up the other 10%

Question 21

What is BMP?

Answer 21

• Bone Morphogenic Protein
• Can induce differentiation of Osteoblasts.

Clinical: Can be given after Orthopedic Surgery to stimulate Bone Growth.

Question 22

What is a Proteoglycan?

Answer 22

Glycosaminoglycans attached to a Protein core.

Question 23

What is Ground Substance made up of?

Answer 23

• Proteoglycans
• Multiadhesive Proteins
• BMP
• Cytokines

Question 24

What are Multiadhesive Proteins?

Answer 24

-Attach cells to mineralized matrix.

2 types:

• Osteonectin: Attaches Collagen to Hydroxyappetite
• Osteopontin: Attaches Cells to Matrix.

Question 25

What is Periosteum?

Answer 25

- Richly vascular layer that surrounds bone. - Contain quiescent cells that still have Osteogenic potential when bone repair is needed. -Periosteum connects to bone via Collagen fibers.

Question 26

What are the 2 different processes of Bone Formation?

Answer 26

-Termed Osteogenesis. 2 Processes: - Intermembranous - Enchondral Intermembranous Formation: - Bone formed directly from Mesenchymal cells with no Cartilage intermediate. - Occurs in Flat bone and during Development of Compact bone. Enchondral Formation: - Hyaline Cartilage is formed from Mesenchymal cells which then gets Calcified. - Occurs at Growth plate during development AND during Fracture healing. - Occurs in Short and Long bones.

Question 27

Describe Fetal Bone Development

Answer 27

- Fetus starts off with Hyaline Cartilage Template (skeleton) - Template covered with Perichondrium. - Blood Vessels invade and a Periosteal collar forms around diaphysis. - This provides stability for the bone. - Calcification of Cartilage begins in the center Diaphysis. This becomes the Primary Ossification center. - Compact bone begins to develop along Diaphysis. - Bone lengthening begins at Epiphyseal growth plate. This is the Secondary Ossification center (The Epiphysis). - Bone replaces cartilage, except at the Articular surface of bone to leave behind Articular Cartilage.

Question 28

Describe the Functional arrangement of Chondrocytes at the Growth Plate.

Answer 28

Resting zone: -Resembles normal Cartilage. Proliferating zone: -Chondrocytes are divided and form linear columns. Hypertrophic zone: -Glycogen rich Chondrocytes Calcified zone: -Chondrocytes that have underwent Apoptosis Ossification zone: - Site where early bone is formed. - Recall Woven (immature) bone is formed first and then remodeled into mature bone.

Question 29

Describe Fracture Healing

Answer 29

- Involves Enchondral Bone formation. - Several stages. Inflammation Stage: - Hematoma (Clot) forms and recruits inflammatory infiltrate. - Growth factors stimulate bone regrowth. Repair Stage: - Fibrocartilaginous (soft) callus forms. - Gets calcified and becomes a hard callus. - Enchondral bone formation makes trabecular bone - Intermembranous bone formation makes compact bone -Woven bone appears first. Remodeling stage: -Woven bone becomes Lamellar bone.