Basic science Flashcards
What type of collagen for Epithelial basement membrane?
Dupuytren’s?
Nucleus polposus?
Articular cartilage?
basement membrane: Type 4
Dupuytren’s: Type 3
Nucleus polposus: Type 2
Articular cartilage: Type 2
How does calcitonin inhibit osteoclasts?
Estrogen?
TGF beta?
Calcitonin: Interacts DIRECTLY with osteoclasts via cell surface raptors***
estrogen: Decreases RANKL* –> thereby stimulates bone production and prevents resorption
Also inhibits activation of adenylyl cyclase*
TGF-beta: Increases OPG***
How does PTH increase action of osteoclast?
1,25 dihydroxy vit D?
PGE2?
PTH: activation of PTH receptor STIMULATES adenylyl cyclase –> more cAMP*
PTH also binds to cell surface receptors on osteoblast to stimulate RANKL production*
1, 25 dihydroxy vitamin D –> stimulates RNKL expression
PGE2: activates adnylyl cyclase
Cell that osteoblasts are derived from?
How make bone?
Osteoblast differentiation?
Osteoblasts from UNDIFFERENTIATE MESNCHYMAL CELLS**
Make bone by producing non-mineralized matrix:
Alk phosphatase
Type I collagen
Osteonectin
Osteocalcin*** –> stimulated by 1,25 dihydroxyvitamin D
Differentiation:
BMP stimulates mesenchymal cells to become osteoprogenitor cells
Core binding factor alpha-1/RUNX2**
Stable beta-catenin plays a major role in inducing cells to form osteoblasts w/ resulting intramembranous bone formation**
PGDF induces osteoblast differentiation
IDGF induces osteoblast differentiation
How does PTH act on osteoblasts to make more osteoclasts?
PTH induces Jagged1 on osteoblasts***
Jagged 1 stimulates Notch receptors on membrane of hematopoietic stem cells –> cell proliferation –> more osteoclasts***
What cell line do osteoclasts come from?
Myeloid hematopoietic cells** –> from MONOCYTE/MACROPHAGE cell line*
Monocyte progenitors fuse tighter to form mature multinuclear osteoclasts***
How do osteoclasts resorb bone?
1: Howship’s lacunae –> sites of bone respiration where ruffled border meets bone surface **
2: Tartrate resistant acid phosphate –> secreted by osteoclasts to lower pH (using carbonic anhydrase) –> increases solubility of hydroxyapatite crystals
3: proteolytic digestion: organic material then removed by CATHEPSIN K (one of major proteolytic enzymes that digest organic matrix at ruffled border)**
How does osteoclast attach to bone?
Attaches at sealing zone***
Via INTEGRINS on osteoclast surface***
alpha-V-beta3 on osteoclast* is receptor for VITRONECTIN on bone surface**
Arg-Gly-Asp (RGD)* sequence of extracellular bone protein –> allows binding to integral on ostoeclast (Ab to to intern or RGD inhibit bone resorption)*
Which osteoprogenitor cells will become:
Osteoblasts?
Cartilage?
Fibrous tissue?
Osteoblasts: Low strain, high O2***
Cartilage: intermediate strain, low O2***
Fibrous: High strain**
What are main stimulators for osteoclast to resorb bone?
RANK-L***
IL-1***
Mesenchymal stem cell will differentiate into which of the following if exposed to:
PPAR-gamma?
MyoD?
Sox9?
C/EBPa
Runx2?
PPAR-gamma: Adipocyte***
MyoD: myoblasts***
Sox9: chondroblasts***
C/EBPa: adipocytes***
Runx2: osteoblasts***
Intermittent PTH tx targets which cells?
Osteoblasts* to form bone
PTH made by parathyroid glands (Chief cells)*** as 115 AA chain that is cleaved to 84 AA’s
Recomb PTH = 1-24 AA sequence at N-terminus***
What protein is most specific for mature osteoblasts but not expressed by immature proliferating osteoblasts?
Osteocalcin***
What is effect of 1, 25 dihydroxy vitamin D3 (active form)
Enzymatic conversion from 25 hydroxy vitamin D3 to 1, 25 dihydroxy vitamin D in kidney***
1,25 –> Increases resportion of Calcium in kidney to increase serum Calcium
Increases excretion of PO4- from kidney (decreases serum phosphate)***
Where is calcitonin made?
Calcitonin made in clear cells in the parafollicles of thyroid gland (C cells)***
Which part of bone is most responsible for compressive strength?
Proteoglycans* and Calcium hydroxyapatite*
type I collagen = TENSILE strength***
Blood supply to bone
What supplies inner 2/3 of mature bone?
Outer 1/3?
Growth plate?
Inner 2/3: arterioles from nutrient artery via aversion system***
Outer 1/3: Periosteal arterioles
Major source to growth plate: Perichondrial artery***
When does limb bud begin to grow?
How does it enlarge?
When can first be noted on transvaginal u/s?
Begins to form at 4 wks***
Enlarges due to interaction between the APICAL ECTODERMAL RIDGE and the MESODERMAL CELLS in the PROGRESS ZONE***
First seen at 8 wks***
What gene helps regulate first steps of limb development?
Notochord expresses Shh*** –> regulates limb bud formation
Limb patterning
Proximodistal?
Radioulnar limb growth?
Timing of radioulnar?
Proximodistal: First signal center to appear is APICAL ECTODERMAL RIDGE –> proximal to distal growth –> defect in AER = proximal limb truncation
FGF’s are needed in AER –> FGF8 is OBLIGATORY for normal limb development
Radioulnar: Second signaling center to appear is ZONE OF POLARIZING ACTIVITY along ulnar/posterior side
Grafting ZPA on anterior/radial side –> mirror image digit duplication***
Shh is dose dependent
High concentration on posterior/ulnar side to have small finger develop*
Low concentration on anterior/radial side for thumb to develop*
Abnormal UPREGULATION of Shh in ZPA = POLYDACTYLY on ULNAR side***
Downregulation = loss of ulnar digits
UPREGULATION on RADIAL side = loss of thumb***
Ulnar side formed earlier than radial side, so disruption of AP patterning will cause loss of later formed elements –> radius/thumb***
Dorsoventral axis embyrology?
Third signaling center (after AER and ZPA) –> non-AER limb ectoderm/WNT signaling center –> Progress zone**
Wnt = dorsal-ventral growth
Hox genes?
A/P or radioulnar patterning along with Shh***
Regulate somatization of the axial skeleton –> digit formation***
What is nucleus polposus from (embryology)?
Annulus fibrosus?
NP: notochord***
Annulus: Sclerotome***
During endochondral ossification at growth plate, what causes the most longitudinal growth of bones?
Chondrocyte HYPERTROPHY***
Not proliferation of chondrocytes***
What would deactivating mutation for PTHrP receptor do to growth plate?
Accelerate maturation in the zone of hypertrophy***
What is groove of Ranvier responsible for?
Perichondral ring?
Appositional bone growth***
Perichondral ring: dense fibrous ring that is critical for overall stability of growth plate***
Which region of physis does collagen type X play a role?
Zone of hypertrophy***
What does sclerostin do?
Sclerostin INHIBITS osteoblasts to DECREASE BONE FORMATION***
Work by binding the Wnt molecule***
How does phosphate administration decrease urinary calcium excretion?
Creates complex w/ calcium in the intestine to decrease available calcium for absorption***
Which BMPs exhibit osteoinductive activity? Which does not?
Which for ALIF?
Which for open tibial shaft?
Nonunion?
What BMP mutation leads to fibrodysplasia ossificans progressiva/stone man dz?
Osteoinductive: BMP 2, 4, 6, 7
BMP 3 = NO osteoinductive activity
BMP2* for ALIF (L2-S1, Medtronic cage), and for open tibia w/in 14 days of fx (IMN only, not plating*)
Nonunion of tibial shaft: BMP-7***
Mutation in BMP 4* = fibordysplasia ossificans progressiva*
How do BMPs work?
Activate mesenchymal cells to transform into osteoblasts –> produce bone***
Activate transmembrane SERINE/THREONINE kinase receptor**** –> SMADs*** (intracellular signaling mediators)
What is the most beneficial ultrasound signal for bone healing?
30mW/cm2 ***
Accelerates fx healing an increases mechanical strength of callus***
How do bone stimulators work:
Direct current?
AC current?
Pulsed EM fields?
Combined magnetic fields?
D/C: decrease osteoclast and increase osteoblast activity by REDUCING O2 tension and INCREASING pH***
A/C: Affect synthesis of cAMP***
Pulsed EM fields: causes CALCIFICATION OF FIBROCARTILAGE***
Combined magnetic fields: elevated concentrations of TGF-beta and BMP***
How does COX2 factor into bone healing?
Promotes fx healing by causing mesenchymal cells to differentiate into osteoblasts***
Fastest to slowest resorption rate for bone graft substitutes?
Calcium sulfate > tricalcxium phosphate > hydroxyapatite**
Osteoconductive vs osteoinductive vs osteogenic?
Osteocondcutive: material acts as STRUCTURAL FRAMEWORK –> DBM
Osteoinductive: Material contains factors that stimulate bone growth and INDCUTION OF STEM CELLS down a bone forming lineage –> BMPs
Osteogenic: Material directly provides cells that will produce bone –> mesenchymal stem cells, osteoblasts and osteocytes
DBM - osteoinductive vs osteoconductive?
BOTH osteoconductive and osteoinductive***
Contains collagen, BMPs***, TGF-beta, calcium
NO mesenchymal precursor cells
What synthetic has the highest compressive strength?
Calcium phosphate graft***
Tricalcxium phosphate, hydroxyapatite***
Shelf life for frozen or freeze dried grafts?
- 20 C: 2 years***
- 70 C: 5 years
Indefinite for freeze dried**
Chance of HIV, Hep C and hep B from fresh frozen allograft?
What are allografts checked for (diseases)?
HIV: 1 : 1,000,000
Hep C - 1 : 100,000
Hep B - 1 : 63,000
Allografts screen for***: HIV HBV HCV HTLV-1 Syphilis
What type of allograft substitute has more serous drainage?
Calcium sulfate***
What type of graft for ACL has the highest antigenicity?
Bone patellar tendon bone graft***
Due to the inclusion of bone***
Even higher than semimembranosus used to recon MCL (extra-articular)**
What to do if ACL graft grows bacteria if cultured during operation and has been implanted into patient?
Observation***
Rates 5-13% but none of studies showed that “contaminated” grafts developed clinical infection***
How often do bulk structural allografts fail due to insufficiency fracture?
Approximately 25% of time**
Anterior vs posterior iliac crest bone grafting?
Higher minor and major complications (significant) with anterior harvest***
Higher pain scores and duration of pain after anterior harvest***
What is lab test to look at vitamin D levels?
25-hydroxyvitamin D3**
What is the inactive form of vitamin D caused by high levels of the active form of vitamin D?
24, 25 dihydroxyvitamin D = inactive form formed in response to high levels of 1, 25 dihydroxyvitamin D***
Sarcomere composition
What happens with contraction to bands?
Thick myosin filaments***
Thin actin filaments***
Bands: H band/zone = myosin only*** I band = actin only*** A band = both actin and myosin*** Z line flanks each sarcomere and acts as site of attachment for actin filament***
During contraction:
A band - stays same length*
Both I band and H zone reduce in length*