Basic Science Flashcards
1
Q
- Compressive strength of bone =
- Tensile strength of bone =
A
- Proteoglycans & Calcium Hydroxyapatite
- Type I collagen
2
Q
Articular/Hyaline Cartilage:
- Isotropic or anisotropic
- Mostly what type of collagen?
- What are the 4 zones? And what is the orientation and appearance of collagen and chondrocytes in each layer?
- what % is water?
- what gives ability to attract water?
- what is responsible for boundary lubrication?
A
- Anisotropic
- Type II
- Superficial zone -
- contains articular cartilage progenitor cells
- highest collagen content
- lowest Proteoglycan content
- High water concentration (*remember superficial is slippery! And deep layer is the inverse)
- Transitional zone
- Deep zone
- round cartilage cells aligned perpendicular to joint surface
- large diameter collagen fibrils
- highest concentration of Proteoglycans
- low water concentration
- Superficial zone -
- /TIDEMARK/ (only if injury passes through this layer there is healing potential)
- Zone of calcified cartilage
- small volume of cells with low metabolic activity
- Zone of calcified cartilage
- 60-85%
- Aggrecan
- HA and Lubricin
3
Q
- Ligament attachment to bone: direct vs indirect
A
- Direct: ligament-fibrocartilage-mineralized fibrocartilage-bone
- Indirect (more common): ligament-mineralized fibrocartilage-periosteum-bone
- MCL attaches indirectly to bone via Sharpey’s fibers (made of Type I collagen)
- Indirect (more common): ligament-mineralized fibrocartilage-periosteum-bone
4
Q
- Muscle motor unit recruitment order during muscle contraction:
A
- Slow-twitch fatigue resistant units (Type I)
- Fast-twitch fatigue resistant units (Type IIa)
- Fast-twitch easily fatigable units (Type IIb)
5
Q
TENDONS
- Tendons detect loading by
- Tendon repair is weakest during the ??? PERIOD, which occurs ??? days following repair.
- Increased training will cause a net increase in Type ?? collagen fibers within tendons
- Decorin regulates the
- Tendons are composed mainly of Collagen Type
- Aggrecan is found in areas of tendon compression and contributes to the
A
- Tendons detect loading by deflection of cell-cilia
- Tendon repair is weakest during the INFLAMMATORY PERIOD, which occurs 5-21 days following repair. During this period neutrophils and macrophages migrate into injury site and release chemotactic factors that recruit fibroblasts
- Increased training will cause a net increase in Type I collagen fibers within tendons
- Decorin regulates the assembly/organization of collagen fibrils and collagen fiber size.
- Tendons are composed mainly of Collagen Type I (95%), and < 5% Type III, V, VI
- Aggrecan is found in areas of tendon compression and contributes to the binding of collagen fibers to specific locations
6
Q
Groove of Ranvier:
A
wedge-shaped zone of cells contiguous with the epiphysis at the periphery that supplies chondrocytes to periphery and is responsible for APPOSITIONAL (width) GROWTH OF PHYSIS.
7
Q
Perichondrial Ring (of La Croix):
A
dense fibrous ring that is a component of physis periphery and critical to stability.
8
Q
enchondral ossification - describe
What type of collagen a/w it?
A
osteoblasts lay down bone on cartilage framework (bone replaces cartilage, cartilage is not converted to bone!)
- * TYPE X COLLAGEN a/w enchondral ossification
9
Q
Main Blood supply to growth plate
A
PERICHONDRIAL artery
10
Q
Heuter-Volkmann Law
A
- COMPRESSION SLOWS longitudinal growth
- TENSION accelerates longitudinal growth
11
Q
Describe the basic science of physeal growth arrest
A
- Physeal growth arrest after physeal injury occurs due to -> vascular invasion across the physis which brings in osteoblasts -> which form a bony bar
12
Q
Name different zones of the growth plate and key facts about each including what disease result for each (see pic in notes)
A
- Epiphysis
- Resting/Reserve Zone: supplies developing cartilage cells
- Proliferative Zone: responsible for LONGITUDINAL GROWTH
- Hypertrophic Zone: contains zone of provisional calcification, zone of maturation, zone of degeneration; and get calcification of matrix (PTHrP and IHh work here)
- Hypertrophic zone is biomechanically the WEAKEST zone of the physics
- **Zone of provisional calcification is location of Salter-Harris fractures (physeal fx) occur through, which is within the hypertrophic zone
- PTHrP delays differentiation of chondrocytes in zone of hypertrophy (w/ loss/mutation of this protein get accelerated maturation in zone of hypertrophy)
- Collagen X plays and important role in this zone for bone mineralization
- Primary Spongiosa: vascular invasion, mineralizes to form woven bone
- Secondary Spongiosa: internal remodeling (replacement of woven bone w/ lamellar bone), external remodeling
- Metaphysis
13
Q
Parathyroid Hormone-related Peptide Stuff:
A
- Ollier’s Syndrome - multiple enchondromas, likely due to mutations of PTH-related protein and Indian Hedgehog (IHh) protein
- Lead toxicity affects growth by inhibiting PTHrP
- PTHrP plays important role in regulation of cell proliferation at the physis and a MAJOR role in maintaining articular cartilage from fetal development to adult life. Physeal chondrocytes regulate PTHrP production via IHh.
14
Q
- Osteoblasts originate from ??? cells
- Osteoclasts originate from ??? cells
A
- Osteoblasts originate from mesenchymal cells
- Osteoclasts originate from myeloid cells
15
Q
Name the 3 things that Osteoblasts secrete and what each do
A
- RANKL: ACTIVATES OSTEOCLASTS, on surface of osteoblast and binds RANK receptor on osteoclast precursors to activate differentiation of mature osteoclast to resorb bone
- OPG: INHIBITS OSTEOCLASTS, binds to RANKL to prevent binding to RANK receptor
- Osteocalcin is only expressed on mature osteoblasts and is the most specific marker of mature osteoblasts, most abundant non-collagenous protein in bone, involved in Ca-homeostasis, during osteoporosis tx serum levels correlate w/ increases in bone mineral density.
16
Q
Besides osteoclasts, what else do Osteoblasts regulate?
A
Osteoblasts regulate hematopoietic stem cells via Jagged/Notch pathway, which is activated by PTH
17
Q
How do osteoclasts bind to bone?
A
- Vitronectin and Fibronectin have the Arg-Gly-Asp sequence on their surface which allow Integrins on the surface of osteoclasts to bind to bone
18
Q
How do osteoclasts resorb bone?
A
- Bone is resorbed by proteolytic digestion by lysosomal enzyme cathepsin K
19
Q
How does Calcitonin work on osteoclasts?
A
- Calcitonin works on osteoclasts by binding them and decreasing osteoclast number and activity and decreases serum Ca.
20
Q
- Wnt pathway stimulates production of bone via:
A
- Wnt binds LRP5/6 (lipoprotein receptor-related protein) -> intracellular cascade that leads to translocation of beta-catenin into the nucleus to activate transcription of genes that control osteoblast differentiation
21
Q
Explain role of Sclerostin and Dickkopf.
How is Sclerostin effected by Vit D?
A
- SCLEROSTIN (SOST in above pic)& Dickkopf (Dkk-1): is osteocyte derived and inhibits Wnt pathway by preventing binding of Wnt to LRP5/6-> leads to INHIBITION OF BONE FORMATION. Part of normal feedback mechanism -> when bone is not loaded (ie go to outer space or during stress shielding), SOST is responsible for the lack of bone formation - it is the chemical link to Wolff’s law!
- With Vit D supplementation 1,25-Vit D and 25-Vit D levels will go up; Sclerostin levels will go down b/c osteocytes have receptors for 1,25-Vit D and those will downregulate sclerostin which will lead to osteoblasts being more active and increased bone formation
22
Q
Indian Hedgehog (Ihh)
A
- Indian Hedgehog (Ihh) - is critically important in osteoblast and chondrocyte differentiation bot prenatally and postnatally.
- In OA osteophytes are formed due to activation of endochondral ossification via Ihh mediation.
23
Q
What are transcription factors? Which ones are * Related to tendons -> * Related to bone -> * Related to cartilage -> * Related to fibroblast -> * Related to T cell and osteoclastogenesis ->
A
- proteins that bind to DNA to activate gene transcription
- Related to tendons -> Scleraxis
- Related to bone -> RUNX2, Osterix
- Related to cartilage -> SOX9
- Related to fibroblast -> Twist1
- Related to T cell and osteoclastogenesis -<> NFATc1 (Nuclear factor of activated T cell, cytoplasmic 1)
24
Q
Describe how bone remodeling works
A
- Bone remodeling of trabecular bone occurs via formation of Howships lacunae (a pit) by osteoclasts - osteoblasts then follow behind and make new bone.
25
Q
- Osteoporosis: diagnosed by ???
Defined by???
A
- Osteoporosis: diagnosed by T-score < -2.5. Defined by decreased bone quantity with normal bone quality
26
Q
Osteopenia
A
- Osteopenia ( = decreased bone mineral density w/o fx risk) : T-score -1 - -2.5
27
Q
T score vs Z score
A
- **BOTH Osteoporosis and Osteopenia are DEFINED BY T SCORE
- Normal bone: T-score > -1
- T-score = comparison to young normals
- Z-score = comparison to age-matched normals (Z same age!)
28
Q
When should you perform bone density screening?
A
- Bone density screening should begin at 65 yo in those with low risk. Others should start earlier (low body wt, chronic steroid use, malabsorption disorders, hx of low impact fx)
29
Q
- Peak bone mass attainment for both men and women is driven by ?
Timing of peak bone mass
A
- Peak bone mass attainment for both men and women is driven by Estrogen
- Timing of peak bone mass varies based on anatomic site - in general 3rd decade of life is the peak
30
Q
What percentage of bone density loss needs to happen before can notice this on XR?
A
bone mineral density loss on XRs can’t be really identified until there has been a 40% loss! - so don’t get fooled by just thinking XRs look okay bc they do for a while despite significant loss!
