FOM 3.1.3 Flashcards
What are is this, what is it stained with and what are the arrows pointing at?
This is hyaline cartilage stained with H and E. The arrows are pointing at chondrocytes in their lacunae.
How does hyaline cartilage accomplish its role as a shock absorber?
Hyaline cartilage functions like a shock absorber or biomechanical spring: solvation water is bound water which interacts with the negatively charged proteoglycans and is squeezed out of cartilage on compression and returns and binds during decompression.
What is the rigidity of the hyaline cartilage dependent on?
Rigidity is dependent on the electrostatic interactions between type II collagen fibrils and the GAGs comprising the proteoglycans resulting in a cross-linked matrix.
What is responsible for rigidity of cartilage?
Type II collagen binding to the proteoglycan aggregate
How is the protein portion of the GAG synthesized and processed?
It is synthesized in the ER and sugars are added to it in the golgi
What is a main differenct between cartilage and bone andhow does this affect the way nutrients are delivered to it?
Cartilage lacks blood vessels, it is AVASCULAR which requires that nutrients and waste seep through the matrix by diffusion.
Deposition of lime salts in the form of hydroxyapatite crystals does what for bone?
It prevents the diffusion of metabolites and prevents interstitial growth, both of these occur in the cartilage
What is are the two types of bone?
Compact bone: dense without cavities
Cancellous (trabecular) bone: 3-dimensional lattice of branching bony spicules, forming trabeculae around marrow spaces
What are the arrows in this picture pointing to?
The top arrows are pointing to cancellous bone and the bottom arrows are pointing to compact bone
What does each of the numbers correspond to?
- Compact bone
- Periosteum
- Marrow cavities
- Trabecular bone
- Epiphysis
- Metaphysis
- Diaphysis
What is the composition of the bone matrix?
Organic Matrix 35% - consisting of 85-90% type I collagen, proteins, glycoproteins
Inorganic Salts - Hydroxyapatite crystals
What is an osteoprogenitor cell and what is its role?
Pluripotent stem cell from mesenchyme. Capable of differentiating into osteogenic cells, osteoblasts. Found in the periosteum and endosteum as bone lining cells in non-growing regions and differentiate into osteoblast following a fracture
What are osteoblasts and what are their role?
These cells synthesize and secrete organic matrix of the bone: types I collagen, non-collagenous protein and alkaline phosphatase.
What are osteocytes?
Osteoblasts that have trapped themselves in calcified matrix
What is an osteoclast?
These are giant multinucleated cells that are derived from monocytes. Produce an acidic environment ideal for the dissolution of bone matrix. These are also said to have a ruffled border
What is the fate of mesenchyme cells in bone?
These become osteoprogenitor cells that develope into osteoblasts and the osteocytes. Also bone lining cells
What is the fate of bone marrow monocyte precursors?
These form monocytes that will form osteoclasts
What is RANK-L?
RANK-L is synthesized by osteoblasts and it is a receptor that stimulates osteoclastogenesis
What is osteoprotegerin?
This is a decoy receptor for RANK-L
What is osteoid and how is it used?
Osteoid is type I collagen and proteoglycans, this is all synthesized by osteoblasts.
What are the main characteristics of an osteoclast?
The ruffled border
The bone matrix
The tight seal
Multiple nuclei
High amounts of lysosomes
What is the periosteum?
Dense connective tissue with osteogenic potential that surrounds the bone. This means there is osteoprogenitor cells comprising the bone lining the outside
What is the endosteum?
It is found lining the marrow cavity and has osteogenic potential. Means there are osteoprogenitor cells that line the inside
What are each of the arrows pointing at?
Blacks lines - bone matrix
Blue arrows - osteocytes
Yellow - Skeletal muscle
Darker green line- periosteum the inner layer is the osteopregenitor cells
Lime green - osteoblasts on the surface of the bone
What is the ARF cycle?
What is the effect of PTH on bone?
Parathyroid hormone produced by the parathyroid gland and functions to increase serum Ca++ levels through several mechanisms shown in the figure. In bone, PTH increases the number of osteoclasts and the ruffled border activity of existing osteoclasts
What is the action of PTH on osteoclasts and osteoblasts?
Osteoblast are exposed to PTH - first effect is to release MCSF leads to increase differentiation of osteocytes from monocyte precursor
Osteoblast then release RANK-L which binds to RANK on osteoclast- binding to osteoclast stimulates ruffled border activity.
Where would you want a drug to target for a disease like osteoperosis where the osteoclasts are winning?
You would want it to target RANK-L
What is osteoprotegerin?
increase removes RANK-L and counteracting the action of the osteoclasts
What are the roles of bisphosphonates?
kill osteoclasts by inducing apoptosis in osteoclasts
Also have a role in inhibiting osteoclast aggregation
What would be another ideal target for treatment of osteoperosis?
Increased expression of osteoprotegerin by osteoblasts
What is M-CSF and what does increasing it do?
Increasing M-CSF increases the number of osteoclasts and increase the activity of osteoclasts
What is the purspose of chondronectin?
Chondronectin promotes adherence of chondrocytes to the matrix
What is the purpose of osteocalcin?
Required for mineralization
The molecular basis for shock absorption within articular cartilage is what?
Hydration of glycosaminoglycans
