Basic Science Flashcards by Jaren LaGreca

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.

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What molecule or signal causes undifferentiated mesenchymal stem cells to differentiate into osteoprogenitor cells?

Runx2

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What is the most specific marker of MATURE osteoblast?

Osteocalcin (stimulated by 1,25(OH) Vitamin D

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What molecule activates osteoclasts?

RANKL

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What molecule binds RANKL to limit its activity (inhibit osteoclasts)?

Osteoprotegrin

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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.

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What antiseptics inhibit osteoblast bone formation?

Hydrogen peroxide, Betadine, Bacitracin

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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

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In relation to osteoblast activity - 1,25(OH) vitamin D3 does what?

Stimulates osteoblast and leads to matrix and alk phos stimulation

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In relation to bone activity - Estrogen does what?

Inhibits bone resorption through Adenylyl cyclase inhibition

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In relation to bone activity - glucocorticoids do what?

Inhibit bone production

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In relation to bone activity - Prostaglandins do what?

Stimulate bone resorption through Adenylyl cyclase

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Osteocytes are former _______

Osteoblasts, which are surrounded by newly formed matrix

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Osteocytes are connected and communicate via __________

Gap junctions

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Osteocytes control extracellular __________ and ________

calcium, phosphorous

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Osteocytes are stimulated by ______ and inhibited by_______

calcitonin (helps absorb extracellular calcium), PTH

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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

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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)

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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

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Wolff’s Law

Remodeling occurs in response to mechanical stress
(The compression side of bone is electronegative, stimulating osteoblasts
(formation))

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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).

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Endochondral bone formation occurs by _________ replacing _________. Two examples are…

bone replacing cartilage. Physeal growth (longitudinal growth) and fracture callous.

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In endochondral bone growth this gene/protein promotes chondrocyte differentiation.

Sox-9

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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.

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.

1. Inflammation 2. Repair 3. 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