Basic Science Flashcards
A southern blot detects….
DNA.
A western blot detects…
protein.
A northern blot detects…
RNA.
siRNA blocks…
mRNA translation.
RT-PCR converts…
RNA to DNA.
Diseases that show anticipation (more severe form of disease at earlier age)
Huntington, myotonic dystrophy, Friedreich ataxia
Imprinting
gene expression (phenotype) occurs from one allele only
Examples of imprinting
Prader-Willi (paternal inheritance)
Angelman (maternal inheritance)
Epigenetics
inheritance by modifying gene expression rather than altering the genetic code
Examples of epigenetics
DNA methylation, histone acetylation/deacetylation
Rheumatoid pathway
T cells produce RANKL causing bone erosion
Cancer cells produce…
RANKL which leads to osteoclastogenesis which is responsible for lytic lesions.
What is responsible for osteolysis around ortho implants?
RANK/RANKL
What molecule is responsible for osteoclast differentiation from monocyte/macrophage lineage?
RANKL
Sclerostin blocks…
the Wnt/BMP pathway which inhibits osteoblastogenesis leading to decreased bone formation.
Gene expression for adipose lineage
PPARy2
Gene expression for cartilage lineage
SOX9
Gene expression for osteoblast lineage
Cbfa1/Runx2
What factor stimulates cartilage regeneration in vitro?
TFG-beta
What factor stimulates tendon and ligament formation?
scleraxis
What factor causes osteolysis around implants?
IL-6
Sunlight helps to synthesize…
VitD3 (cholecalciferol) on the skin surface which leads to hydroxylation in the liver to 25-OH VitD3 (25-hydroxyvitaminD3) whith then gets hydroxylated again in the kidney to 1-25(OH) or calcitrol
Active form of vitamin D
1,25-dihydroxyvitaim D3
Lab test for vitamin D deficiency is…
25-hydroxyvitamin D3.
Vitamin D increases serum…
calcium and phosphate while PTH (from chief cells of parathyroid glands) increases calcium and decreases phosphate.
Limb buds are first seen at…
8 weeks of gestation
what gene regulates limb bud formation/development?
sonic hedge-hog
the zone of polarizing activity controls…
AP axis (radioulnar axis, or thumb to SF, great toe to small toe)
The apical ectodermal ridge controls…
longitudinal limb growth.
Wnt controls…
dorsoventral axis development.
Wolff law
bone remodels in response to mechanical stress applied to it
Intramembranous bone formation
the no cartilage model
flat bones, physeal growth, primary bone healing (haversian remodeling), with absolute stability
Primary bone healing involves…
cutting cones, osteoclasts and osteoblasts remodeling lamellar bone
Cleidocrainal dysplasia is caused by…
Cbfa1/Runx2 mutation leading to dysfunction of intramembranous ossification.
Endochondral bone formation
cartilage model
long bones, 2ndary bone healing with relative stability. Callus formation
What initiates the SMAD signaling pathway?
BMP binds to serine/threonine kinase receptor
BMPs induce…
host progenitor cell migration and differentiation at fracture sites (inflammatory stage of fx healing).
BMP2 is FDA approved for…
acute open tibia fractures after IMN and ALIF.
BMP2 is the best alternative to…
iliac crest autograft.
BMP2 is involved in…
chondrogenic differentiation from mesenchymal cells.
BMPs 5, 6, and 7 are involved in…
osteoinduction and osteogenesis.
BMP7 is FDA approved for…
long bone nonunion and posterolateral lumbar fusion.
Which BMP has no osteoinductive potential?
BMP3
What factor is important in the apoptosis of interdigital web spaces during development?
BMP
Osteoclasts are derived from…
monocyte/macrophage lineage.
When PTH binds to a PTH receptor on an osteoblast, then…
the osteoblast secretes RANKL which leads to RANKL binding RANK on an osteoclast leading to bone resorption.
What secretes osteoprotegerin?
osteoblasts
OPG binds…
RANKL which inhibits osteoclast activity.
Bone resorption at Howship’s lacunae
ruffled border of osteoclast attaches to the bone surface –> integrin on osteoclast binds to vibronectin on bone surface
Vibronectin contains…
Arg-Gly-Asp (RGD) sequence, which is an integrin recognition sequence.
Carbonic anhydrase acts to…
lower pH of Howship’s lacunae and cathepsin K breaks down organic bone matrix.
Bone gets its compressive strength from…
proteoglycans and calcium hydroxyapatite.
Bone gets its tensile strength from…
type I collagen.
What supplies the outer 1/3 of the diaphysis blood supply?
periosteal arterioles
What blood sources supplies the inner 2/3 of bone (60% of cortical bone of a long bone)?
nutrient artery
What supplies the growth plate?
Perichondral artery
Cancellous chips properties
osteoconductive
DBM properties
osteoconductive and osteoinductive
MOA of bone stimulator
electrical stimulation –> upregulation of TGF-beta and BMPs
What is the relevance of the proliferative zone?
Chrondrocyte proliferation
**Achondroplasia is affected by this zone.
The hypertrophic zone is made up of…
zones of maturation, degeneration, and provisional calcification.
What is the importance of the zone of provisional calcification?
chondrocyte death, matrix calcification (type X collagen is important)
Which growth plate zone is affected in SCFE and salter harris fractures?
hypertrophic zone
What growth plate zone is affected in rickets?
zone of provisional calcification
What zone of the growth plate is affected in scurvy?
primary spongiosa (metaphysis)
The groove of ranvier is important for….
appositional growth of the long bone.
Collagen restrains the swelling pressure of…
aggrecan in articular cartilage.
Which structures are predominantly type I collagen?
- bone
- tendon
- ligament
- meniscus
- fibrocartilage
- annulus fibrosis
What structures are predominantly type II collagen?
- articular cartilage
- nucleus pulposus
The superficial zone of articular cartilage has…
high collagen and low proteoglycan. The chondrocytes are flat and collagen fibers oriented parallel to the joint surface.
What zone of cartilage are the chondrocyte progenitor cells located in?
superficial zone
In the deep zone of articular cartilage, the chondrocytes are…
round. Collagen fibers are oriented perpendicular to the joint surface. This layer has highest proteoglycan content.
The tidemark separates…
articular cartilage form subchondral bone.
Articular cartilage only heals if…
injury crosses the tidemark into the subchondral bone.
With advanced age, articular cartilage becomes…
more brittle bc of increase in glycation end products.
in the spine, aging leads to conversion of…
disc to fibrocartilage and an increase keratin sulfate to chondroitin sulfate ratio.
PTHrP is important in the maintenance of…
articular cartilage phenotype during growth and development.
What type of cells produce synovial fluid?
type B
Prolonged non-weight bearing results in..
cartilage thinning
The annulus fibrosus is derived from…
mesoderm (sclerotomal cells).
The nucleus pulposus is derived from…
the notochord.
The nucleus pulposus has the highest…
proteoglycan content (low collagen to proteoglycan ratio)
With aging, size and cellualrity of the nucleus pulposus…
decreases. So does aggrecan.
Disc degeneration is associated with…
increased fibronectin fragmentation and proteoglycan fragmentation.
Greatest risk factor for degeneration of the disc is…
genetics.
Disc degeneration is associated with…
increase in collagen I and decrease in collagen II.
Type I muscle fibers
slow twitch
red
low activation threshold and therefore are recruited first
aerobic/oxidative
Type II muscle fibers
fast twitch
white
anaerobic/glycolytic
aerobic activity lasting < 10 seconds utilizes…
ATP and creatine phosphate for energy
Aerobic activity lasting longer than 4 minutes gets muscle energy from…
glycogen an dfatty acids.