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MSK/Derm > Bone Physiology - Endocrine > Flashcards

Bone Physiology - Endocrine Flashcards

1
Q

What are the six important roles the skeleton plays?

A

support

protection

movement

blood cell production

mineral stores

endocrine control

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2
Q

What characteristic of cancellous bone gives rise to its strength?

A

the cross struts that are intrinsically part of its structure

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3
Q

What bone do the neural crest cells give rise to? The sclerotome? The lateral plate mesoderm?

A

neural crest - craniofacial bone

sclerotone - most axial skeletons

lateral plate mesoderm - limb mesenchyme

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4
Q

What are the properties of the mineral phase of bone?

A

nano-crystalline and highly substituted analog of the naturally occurring mineral hydroxylapatite

major substituents are carbonate, magnesium, and acid phosphate, along with other trace elements the content of which depends on diet and environment

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5
Q

What are the cellular constituents of the skeleton?

A

chondrocytes

osteoblasts

osteocytes

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6
Q

Describe the differentiation and formation of osteoclasts.

A

a member of the monocytehacrophage family and a polykaryon that can be generated in vitro from mononuclear phagocyte precursors

principal physiological osteoclast precursor is the bone marrow macrophage

hematopoietic stem cell commits after expression of PU.1

after a series of differentiation, they fuse and form giant cells

they then attach to bone and lead to bone resorption

can also release bone-derived factors to communicate with other cells, the osteoblasts

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7
Q

What is the action of osteoclasts?

A

resorbs bone by secreting acid to degrade the structure

acid hydrolases and other ensymes allow for the generation and secretion of acid

generates hydrogen ions through carbonic anhydrase 2

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8
Q

What is the cross-talk between principal bone cells?

A

resorption of specific bone matrix releases factors that regulate the cells

direct cell to cell contact: OB derived: Osteoprotegerin-RANKL and ephrine

synthetic products from each cell influence the other cell - paracrine signaling

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9
Q

What are the two cytokines essential and sufficient for basa osteoclastogenesis?

A

RANKL and macrophage colony stimulating factor (M-CSF or CSF-1)

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10
Q

What is RANKL and what is its role?

A

paracrine molecule that allows osteoblast control of osteoclastic acivity

soluble RANKL goes to a mature osteoclast, which expresses the receptor called RANK

when RANKL binds to RANK, the osteoclast resorbs bone

osteocytes in bone can also secrete RNAKL and influence the osteocyte

circulating soluble RANKL can also go to a precursor osteoclast and cause it to differentiate and mature

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11
Q

What is the function of M-CSF?

A

contributes to the proliferation, survival, and differentiation of osteoclast precursors

also important for the survival and cytoskeletal rearrangement required for efficient bone resorption

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12
Q

What is the role of OPG?

A

osteoprotegerin - decoy receptor

if RANKL binds to OPG, then it blocks the function of the molecule

this shuts off the cell - an osteoclast bound with OPG is not active and won’t have more precursor cells

osteoblast can present RANKL or OPG directly to precursor cells

can also bind directly to RANKL

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13
Q

What is the signaling pathway of the RANK receptor?

A

activates TRAF-6 and a signaling cascade results in differentiation or anti-apoptosis and cytoskeletal reorganization (through Akt)

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14
Q

What happens when OPG is upregulated?

A

the differentiation of new osteoclasts is limited, and bone becomes much more dense because no bone is being resorbed

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15
Q

What happens when OPG is knocked out?

A

there is too much differentiation and bone resorption, which results in brittle bones and lack of structure

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16
Q

What happens when RANKL is knocked out?

A

the phenotype is the same as the OPG upregulation

lack of differentiation and bone resorption

17
Q

What happens when RANK is knocked out?

A

same phenotype as RANKL knockout and OPG upregulation

lack of signaling will lead to higher bone density and lack of osteoclast differentiation

18
Q

What are the cytokines involved in osteoblast differentiation?

A

Hedgehogs

bone morphogenetic proteins (BMPs)

TGF-P

PTH

WNTs

19
Q

stages of osteoblast differentiation

A

proliferation

extracellular matrix deposition

matrix maturation

mineralization

20
Q

What are the roles of osteocytes?

A

cell body with long dendritic processes that end on right on the capillary in the bone as though these tentacles are neuro-sensing

mechanosensor

transducer

biosynthetic factor

21
Q

How is the osteocyte activated?

A

mechanosensor

shear stress leads to opening of channels and activation of receptors that lead to more osteoblast formation

osteoclasts are downregulated in these cases

Wnt signaling pathway is important

increased OPG, decreased RANKL promoting bone formation

22
Q

What is the role of sclerostin and what is its signaling pathway?

A

sclerostins are products of the signaling pathways that shuts off osteoblasts

when it is not active, there is osteoblast activity

presence of sclerostin is a way to inactivate the osteoblast

signaling through activation of a membrane receptor that leads to activation of the APC complex

23
Q

Describe the progression of bone growth as we age.

A

initial increase in bone mass, peak is round 20 years of age

preserved for abut 30-40 years until it begins to decrease

after a certain point, there is a increasing risk of a spontaneous fracture

bone also grows linearly, which makes the teenage years a risk for fracture as well because the middle of the bone is yet to be filled in

24
Q

What happens during bone modeling?

A

bone is hollowed out, marrow cavity grows larger, bone lengthens

osteoblastic bone progression, endocortical surface made larger by osteoclasts

osteoblasts are on the outer surface

25
Q

How does the geometry and strength of bone change as it grows?

A

mass remains the same

density remains the same

strength increases dramatically

26
Q

What is the process of remodeling?

A

maintains skeletal integrity of structure and density

single-surface phenomenon

osteocytes recruits osteoclasts to the surface of bone

osteoclasts resorbs bone to a specified depth and stops

osteoblasts then come in, and with the help of vitamin and calcium, the bone is filled in again

resorption is fast, and reversal and formation take longer

in healthy people, remodeling 3-4% of entire bone surface at any given time

most bone pathology increases rate of remodeling - bad outcomes

27
Q

What is osteoid?

A

the organic component of bone

28% is type I collagen

5% is non-collagen structural proteins such as proteoglycans, sialoproteins, Gla-containing proteins, phosphoproteins, and bone-specific proteins such as osteocalcin and osteonectin

28
Q

What senses calcium levels, and what is the response?

A

calcium receptor in the parathyroid hormones

when calcium is low, sensor stimulates release of PTH

this activates vitamin D in the kidney and decreases excretion of calcium

increases release of calcium from bone and absorption of calcium from the intestines

29
Q

What factors downregulates secretion of pHT?

A

high blood calcium levels

high levels of 1,25D

FGF23 inhibits transcription and subsequent release

30
Q

What are some new concepts in bone biology in regards to bone function?

A

glucose homeostasis through osteocalciun

male fertility through osteocalcin

31
Q

What is the effect of estrogen on bone?

A

increased osteoclast activity

decreased osteoclast apoptosis - leads to bond growth, maturation, and maintenance

32
Q

What is the effect of androgens on the bone?

A

inhibits osteoclast activity

inhibits osteoblast apoptosis

increases osteoblast proliferation and differentiation

leads to bone growth, maturation, and maintenance

33
Q

What is the role of osteocalcin? Describe its signaling pathway.

A

bone secretes osteocalcin

Gprc6a receptor binds and leads to spermatogenesis and germ cell survival through high cAMP

testosterone from the testes will promote osteocalcin production

osteocalcin made by osteoblasts also regulates whole-body insulin insensitivity - tells the pancreas to handle glucose appropriately

34
Q

What are the common posttranslational modifications of collagen in bone?

A

1) hydroxylation of certain lysyl or prolyl residues
2) glycosylation of the hydroxylysine with glucose or galactose residues or both
3) addition of mannose at the propeptide termini
4) formation of intra- and intermolecular covalent cross-links that differ from those found in soft connective tissues

MSK/Derm (54 decks)

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