Basic Science Flashcards
Higher Young’s Modulus of elasticity means what?
MORE STIFFNESS
Young’s modulus is a measure of the ability of a material to withstand changes in length when under lengthwise tension or compression. Equal to the longitudinal stress divided by the strain.
What molecule or signal causes undifferentiated mesenchymal stem cells to differentiate into osteoprogenitor cells?
Runx2
What is the most specific marker of MATURE osteoblast?
Osteocalcin (stimulated by 1,25(OH) Vitamin D
What molecule activates osteoclasts?
RANKL
What molecule binds RANKL to limit its activity (inhibit osteoclasts)?
Osteoprotegrin
What molecule inhibits osteoblasts?
Sclerostin
- Sclerostin sequesters Wnts which are signaling molecules that promote osteoblast bone formation
- Sclerostin secretion is based on mechanical loading, decreased sclerostin in high areas of strain.
What antiseptics inhibit osteoblast bone formation?
Hydrogen peroxide, Betadine, Bacitracin
In relation to osteoblast activity - pulsatile PTH does what?
Stimulates osteoblast by producing Alk phos and Type I collagen
*High levels of PTH signal release of RANKL
In relation to osteoblast activity - 1,25(OH) vitamin D3 does what?
Stimulates osteoblast and leads to matrix and alk phos stimulation
In relation to bone activity - Estrogen does what?
Inhibits bone resorption through Adenylyl cyclase inhibition
In relation to bone activity - glucocorticoids do what?
Inhibit bone production
In relation to bone activity - Prostaglandins do what?
Stimulate bone resorption through Adenylyl cyclase
Osteocytes are former _______
Osteoblasts, which are surrounded by newly formed matrix
Osteocytes are connected and communicate via __________
Gap junctions
Osteocytes control extracellular __________ and ________
calcium, phosphorous
Osteocytes are stimulated by ______ and inhibited by_______
calcitonin (helps absorb extracellular calcium), PTH
Osteoclasts resorb bone by…
Binding _______
Increasing __________
Synthesizing__________
Binding bone surface through integrins (specifically αvβ3 or vitronectin receptor), having a “Ruffled border” to increase the surface area of resorption, synthesizing TRAP (tartrate-resistant acid phosphate - lowers pH utilizing carbonic anhydrase and thus increases solubility of hydroxyapatite crystals), cathepsin K, MMPs, lysosomal cysteine proteinases
RANKL is released by _________ and has a receptor on __________ and functions to _______. Lastly, RANKL is inhibited by _________.
osteoblasts, osteoclast precursor cells, activate them into mature osteocytes leading to bone resorption, osteoprotegerin (OPG)
Does activation of the following signaling molecules promote bone formation or resorption? RANKL Calcitonin IL-1 IL-10 Bisphoshonates 1,25 dihydroxy vitamin D Prostaglandin E2 IL-6 MIP-1A OPG (osteoprotegerin) Estrogen TGF beta
RANKL - resorption (binds to RANK receptor on osteoclasts)
Calcitonin - formation (inhibits osteoclasts by interacting with osteoclast surface receptors)
IL-1 - resorption (stimulates osteoclast differentiation)
IL-10 - formation
Bisphoshonates - formation
1,25 dihydroxy vitamin D - resportion (stimulates RANKL)
Prostaglandin E2 - resorption (activates adenylyl cyclase)
IL-6 resorption (myeoloma)
MIP-1A - resorption (myeoloma)
OPG - formation (sequesters RANKL)
Estrogen - formation (decrease RANKL)
TGF beta - formation
Wolff’s Law
Remodeling occurs in response to mechanical stress
(The compression side of bone is electronegative, stimulating osteoblasts
(formation))
Hueter-Volkmann law
Mechanical loading can influence the rate of growth.
-Compressive forces inhibit growth (gymnasts tend to be shorter); tension stimulates it
This type of remodeling occurs in small packets of cells
known as basic multicellular units (BMUs).
Endochondral bone formation occurs by _________ replacing _________. Two examples are…
bone replacing cartilage. Physeal growth (longitudinal growth) and fracture callous.
In endochondral bone growth this gene/protein promotes chondrocyte differentiation.
Sox-9
The zones of physeal growth
Reserve: cells store lipids and proteoglycans.
Proliferative: cellular proliferation and stacking of chondrocytes.
Hypertrophic
-Maturation: Chondrocytes increase 5x in size, accumulate calcium in their mitochondria.
-Degeneration: Chondrocytes die.
-Provisional Calcification: Chondrocytes release calcium.
*Osteoblasts then migrate from sinusoidal vessels and replace cartilage as scaffolding for bone formation.
___________ inhibits chondrocyte maturation.
PTHrP
Subsequently IHH is produced by chondrocytes and regulates the expression of PTHrP (PTH related peptide).
In the hypertrophic zone of the physis, Type _____ collagen is produced by chondrocytes and is important for mineralization.
X
Attach the disease with its respective pathologic area within the physis.
Gaucher’s
Diastrophic Dysplasia
Reserve zone
*where cells store lipids and proteoglycans.
Attach the disease with its respective pathologic area within the physis.
Achondroplasia
Gigantism
Multiple Hereditary Exostosis
Proliferative zone
Attach the disease with its respective pathologic area within the physis.
Hypertrophic zone, specifically the maturation zone.
SCFE
Attach the disease with its respective pathologic area within the physis.
Hypertrophic zone, specifically the Degenerative zone.
Rickets
Attach the disease with its respective pathologic area within the physis.
Hypertrophic zone, specifically the Provisional Calcification zone.
Salter Harris Fx
Attach the disease with its respective pathologic area within the bone.
Corner Fx
Scurvy
Primary spongiosa
Name type of fracture healing based on the characteristic: <2% strain
Primary bone healing
Name type of fracture healing based on the characteristic: intramembranous via haversian remodeling (cutting cones)
Primary bone healing
Name type of fracture healing based on the characteristic: absolute stability (ie. compression plating)
Primary bone healing
Name type of fracture healing based on the characteristic: <10% strain
Secondary bone healing
Name type of fracture healing based on the characteristic: Enchondral via callous (cartilage model)
Secondary bone healing
Name type of fracture healing based on the characteristic: relative stability (IMN, ex-fix, cast)
Secondary bone healing
Name the 3 stages of fracture healing.
- Inflammation
- Repair
- Remodeling
Name the stage of fracture healing:
- Hematoma -> Macrophages, neutrophils & cytokines (PDGF, TNF-alpha, TGF-beta, IL-1, IL-6)
- Fibroblasts form granulation tissue, mesenchymal stem cells -> osteoblasts via runx-2/osterix
Inflammation stage
Name the stage of fracture healing:
- Soft callous -> Primary callous (woven bone) via enchondralossification, within 2 weeks
- Type II cartilage (soft callous), Type I cartilage (bone)
- Low strain -> osteoblastic signaling; High strain -> chondrocyte signaling
- Amount of callous inversely related to immobilization
Repair stage
Name the stage of fracture healing:
-Hypertrophic chondrocytes calcify extracellular matrix via proteases and Type X collagen
-Multiple factors are expressed as bone is formed including BMPs, TGF-Betas, IGFs, osteocalcin,
collagen I, V and XI
-New bone remodeled by osteoblasts/ osteoclasts; woven bone replaced by lamellar and shaped through Wolff’s Law
Remodeling phase
What is the most important factor for fracture healing?
Blood supply, which peaks at 2 weeks.
This synthetic bone graft has high compressive strength, degrades slowly, is osteoconductive and uncludes hydroxyapatite…
Calcium phosphate
Level I evidence shows that calcium-phosphate bone substitutes allow for bone defect filling, early rehabilitation, and prevention of articular subsidence in distal radius and tibial plateau fractures
T score of osteopenia
-1 to -2.5
Indications for pharmacologic treatment of osteopenia or osteoporosis.
Postmenopausal women and men >50 yo with:
- hip/vertebral body fx
- T-score between -1.0 and -2.5 at femoral neck or spine and 10 year risk of hip fracture >3% or FRAX score >20%
- T-score
MOA of denosumab
Antibody that binds RANKL and prevents osteoclast activation
MOA of Teraperatide (Forteo)
Essentially a recombinant PTH that binds receptors on osteoblasts and promotes ANABOLIC bone formation.
Risks: transient hypercalcemia, Paget’s disease -> osteosarcoma
BMP____ is directly responsible for osteoinduction and osteogenesis.
BMP2
Why is Rifampin commonly used synergistically with other antibiotics?
It has great potential to penetrate cells.
- Rifampin is lipophilic and can easily cross cellular walls and membranes to exert its bactericidal action to block RNA polymerase and subsequent RNA transcription.
- Effective against intracellular phagocytized Staph aureus.
MOA of Rivaroxaban
Selective factor 10a inhibitor
MOA of Aspirin
Cyclooxygenase inhibitor which reduces thromboxane A2.
MOA of Warfarin
Vitamin K antagonist and reduces the production of clotting factors II, VII, IX, X
MOA of Heparin/LMWH
Activation of antithrombin III which then inhibits the clotting factors IIa, III, Xa
Tendons are 95% Type ______ collagen
Type I collagen. The remaining 5% is proteoglycans and small mix of other collagen types (mostly collagen type III). Proteoglycans help keep water content in tendons (Decorin is most common proteoglycan found in tendons).
Osteoblasts synthesize Type _______ collagen
Type 1 collagen
PTH binds _______ which secrete secondary messanger molecule to activate _______
osteoblasts; osteoclasts
Bone is compose of Type ___ colllagen
Type 1
bONE
_______ is the major determinant of fracture healing and peaks at _______ weeks
Blood flow; 2 weeks
