Msk: Bone Physio And Biochem

Front 1

what portion of bone is organic and what portion is inorganic

Back 1

1/3 is organic and 2/3 is inorganic

Front 2

what constitues the organic portion of bone

Back 2

85% is collagen, the rest is non-collagenous proteins, proteoglycans and lipids (0.1%)

Front 3

what is the most abundant type of collagen in bone

Back 3

type I

Front 4

what is the purpose of collagen in bone

Back 4

provides tensile strength

Front 5

describe the physical (not aa) structure of type I collagen

Back 5

left handed triple helical supercoil that is made up of two identical alpha1 chains and one alpha2 chain

Front 6

describe the aa sequence of type 1 collagen

Back 6

glycine-proline-hydroxyproline (gly-pro-hypro) repeated

Front 7

what can be measured as an indicator of bone resorption

Back 7

hydroxyproline in the urine (from collagen degradation) although diet can affect it, more specific markers urinary are urinary excretion of the collagen pyridinoline and deoxypyridinoline crosslinks (deoxy is specific for bone)

Front 8

what aa's are required for intra and intermolecular crosslinks of or within collagen triple helices

Back 8

lysine and hydroxylysine

Front 9

how does type I collagen vary between tissues (e.g. btwn cartilage and bone)

Back 9

the number and variety of crosslinks (e.g. cartilage has a lot of crosslinks btwn 2 hydroxylysines and bone has more crosslinks btwn lysine and hydroxylysine)

Front 10

the _____ crosslinks are the ones most critical for normal bone mineralization

Back 10

the INTERMOLECULAR crosslinks are the ones most critical for normal bone mineralization

Front 11

many of the serum derived proteins in bone are ___ (acidic/basic) and bind to the ____ of bone

Back 11

many of the serum derived proteins in bone are ACIDIC and bind to the HYDROXYAPATITE of bone (mineral portion of bone)

Front 12

non-collagenous proteins in bone come from which two sources

Back 12

serum or secreted by osteoblasts

Front 13

what are the 3 major groups of non-collagenous proteins

Back 13

1) cell attachment and Ca binding proteins
2) gamma carboxylated proteins (Gla)
3) growth and differentiation related

Front 14

what is the function of cell attachment and Ca binding proteins

Back 14

help mediate cell to cell signaling (e.g. fibronectin, thrombospondin, osteopontin) and can serve as points of attachment for osteoblasts and osteoclasts via integrins

Front 15

what is osteocalcin

Back 15

a gamma carboxylated protein (bone Gla protein, ie BPG), may function as a signal during bone turnover, its syn is stimulated by 1,25 dihydroxyvit D

Front 16

what are examples of growth and differentiation related non-collagenous proteins,where do they come from, and what is their function

Back 16

TGF-a and IGF-1, secreted by osteoblasts to stimulate osteoblast cell division and matrix expression

Front 17

___ is the hallmark of the osteoblast phenotype and is synthesized and secreted in high levels

Back 17

alkaline phosphatase (note: its function is still undefined but it may be involved in initiation of mineralization in collagen fibrils)

Front 18

what are the 2 types of GAGs that are attached to protein cores in bone

Back 18

chondroitin sulfate and heparin sulfate

Front 19

function of chondroitin sulfate containing proteoglycans

Back 19

maintain integrity of osteoblast pericellular env and integrity of newly deposited bone matrix (Chondroitins are the Caretakes of osteoblasts)

Front 20

function of heparin sulfate containing proteoglycans

Back 20

membrane associated and may facilitate assoc of osteoblasts with other matrix molecules like attachment and growth factors

Front 21

what are the components of the lipid portion of bone

Back 21

TGs, FFAs, phospholipids, and cholesterol

Front 22

what is the role of lipids in bone

Back 22

some provided structural integrity to cell membrane, and role for ossification and maintenance of a normal skelton

Front 23

what is the mineral in bone composed of and what is it's purpose

Back 23

primarily Ca and PO4 (minor components are Mg, Na, and K) and it protects the organic matrix from degradation

Front 24

how does the water content of bone change as you age

Back 24

the water is lost and replaced by mineral as bone ages

Front 25

how is the organic and inorganic matrix arranged and what is the advangtage of this

Back 25

adajacent collagen fibrils are arranged in overlap and stagger orientation which creates holes for the mineral crystals to be deposited w/o changing the shape of the fibrils (hence bone mineral is deposited at specific regions along collagen)

Front 26

bone formation is a 2 step process that involves ___ and ___

Back 26

matrix formation and subsequent mineralization

Front 27

the ____ in osteoblasts are involved in the storage and transport of intracellular Ca and may pla a role in mineralization

Back 27

mitochondria

Front 28

two specific functions of osteoblasts

Back 28

secrete procollagen to form osteoid, store Ca and PO4

Front 29

what comprises the maturation period of osteoid matrix

Back 29

the last 2 stages of collagen synthesis in which collagen cross linking occurs

Front 30

give the basic steps of bone formation starting with collagen

Back 30

collagen syn--> collagen crosslinking--> thickening osteoid seam matures--> mineralization lag time (delay of 5-10 days in adults) --> deposition of mineral

Front 31

scurvy is caused by a deficiency of ___ that prevents ____ resulting in decreased quantity and quality of ___

Back 31

scurvy is caused by a deficiency of VIT C that prevents HYDROXYLATION OF PROLINE AND LYSINE resulting in decreased quantity and quality of COLLAGEN

Front 32

what are the manifestations of scurvy

Back 32

new bone formation is prevented and old bones become brittle (also old scar tissue and wounds tend to rupture more easily)

Front 33

what is the classical clinical picture of ehlers danlos syndrome

Back 33

hyperextensible joints, hyperelastic skin, poor wound healing, easy bruising (due to delicate collagen fibers in mult locations)

Front 34

in bone mineralization, the first step in the precipitation of bone salts involves ___ in which a core seed crystal of ___ is deposited

Back 34

in bone mineralization, the first step in the precipitation of bone salts involves NUCLEATION in which a core seed crystal of HYDROXYAPATITE is deposited (this process may be controlled by osteoblasts, but they are still unsure)

Front 35

functions of osteocytes

Back 35

syn collagen, control bone mineralization within their space, carry out bone resorption (osteocytic osteolysis), and act as a mechanosensor in bone homeostasis

Front 36

what are osteocytes derived from

Back 36

osteoblasts that have become encased in calcified bone

Front 37

what are the 3 osteoclast organelles involved in bone resoprtion

Back 37

mitochondria, lysosomal enzymes, and a ruffled brush border

Front 38

bone resorption involved what 2 big picture evens

Back 38

dissolution of bone mineral and collagen hydrolysis

Front 39

describe the steps of bone resorption

Back 39

1) osteoclasts secrete acid hydrolyases that are released onto the bone resorptive surface
2) a sealing zone is created btwn the bone and the osteoclast ruffled border membrane
3) osteoclasts secrete protons within the sealing zone (via ATPase proton pump) to create an acidic environment to facilitate resorption
4) mineral crystal dissolution begins
5) matrix now exposed to collangeolytic enzymes called MMPs (matrix metalloproteinases) which are secreted by osteoclasts
6) MMPs act on the insoluble organic matix to create soluble fragments
7) the fragments are further degraded, internalized into lysosomes and transfered to the basolateral surface of the osteoclasts
8) the above processes promote mobilization of Ca and PO4 from bone to fluid compartment and replacement of old matrix with new matrix

Front 40

what controls the bone remodeling process

Back 40

bone multicellular unit (BMU)

Front 41

basic steps of bone remodeling

Back 41

1) activation stimulus like parathyroid hormone
2) area of bone is covered by lining cells
3) osteoclasts recruited and resorb bone
4) reversal phase
5) influx of osteoblasts that syn and mineralize new bone matrix

Front 42

where does bone resoprtion occur in cortical bone

Back 42

a cutting cone of osteoclasts (since coricol bone has lot of mass but little surface area it has to cut into bone)

Front 43

where does bone resorption occur in trabecular bone

Back 43

resorption cavities called howship lacunae (on the surface of bone)

Front 44

what is the primary source of new osteoclasts

Back 44

hematopoetic stem cells of the bone marrow

Front 45

what is the primary source of new osteoblasts

Back 45

either local CT mesenchymal cells or bone marrow stromal stem cells

Front 46

what do active osteoblasts produce during perioids of bone formation

Back 46

alkaline phosphatase and osteocalcin (hence they can be used as markers for bone formation)

Front 47

what assay is used to monitor bone resorption

Back 47

one that detects fragments of osteocalcin (when bone is resorbed, fragments of osteocalcin are released into the blood)

Front 48

what form is most of the body Ca in

Back 48

hydroxyapatite

Front 49

where do major Ca fluxes occur

Back 49

btwn the serum and exchangable fraction of bone (min 6g Ca/day in each direction)

Front 50

T/F: Ca influx into bone is not metabolically controlled

Back 50

TRUE! the efflux is metabolically controlled (ie small changes in efflux are buffered by changes in bone remodeling, intestinal absorption and renal reabsorption)

Front 51

when serum Ca levels are low, ___ induces a rapid elevation in ___

Back 51

when serum Ca levels are low, PTH induces a rapid elevation in efflux from bone

Front 52

what is the bone fluid compartment

Back 52

a fluid compartment between bone lining cells and bone that has a large supply of Ca (relatively limitless supply), Ca is transferred from here to the extracellular fluid via ATPAse

Front 53

T/F: the bone fluid has only small discrete amount of Ca

Back 53

FALSE- it has a relatively limitless supply of Ca

Front 54

hyperparathyroidism results in hyper or hypocalcemia

Back 54

hyper (PTH causes efflux of Ca from bone)

Front 55

what is the function of 1,25 dyhydroxy vit D

Back 55

stimulates intestinal Ca absorption

Front 56

what regulates levels of 1,25 dyhydroxy vit D

Back 56

PTH

Front 57

does 1,25 duhydrocy vit D provide rapid or long term control of Ca levels

Back 57

long term (it has a slow feedback mechanism)

Front 58

what is the function of calcitonin

Back 58

buffers Ca spikes/anti-hypercalcemic agent (note: its role remains unresolved though)

Front 59

list the sources of Ca utilized when serum Ca is low, from early to late

Back 59

1) extracellular fluid from ATPase pumping system around bone lining cells
2) surface in contact with bone fluid
3) resoprtion from all regions of bone via osteoclasts

Front 60

where do osteocytes live and how to they communicate btwn one another

Back 60

live in lacunae and communicate via canaliculi

Front 61

which bone cells are the most impt for Ca homeostatsis

Back 61

osteocytes

Front 62

what bone cell initiates bone resorption

Back 62

osteoblasts (they are the ones with PTH receptors)