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Applied Biochem > Biochem - Osteoclasts, Osteoporosis, and Fracture Healing > Flashcards

Biochem - Osteoclasts, Osteoporosis, and Fracture Healing Flashcards

1
Q

Bone Remodeling

A

continual bone repair from damage being removed by osteoclasts and rebuilt by osteoblasts

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2
Q

Osteoclasts are derived from

A

same precursors as macrophages (hematopoietic lineage)

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3
Q

Mature osteoclasts are

A

multinucleated

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4
Q

Osteoclasts express proteases for….

A

removing ECM proteins like collagen

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5
Q

Osteoclasts express proteins that act as proton pumps which:

A

generate H+ ions (reducing pH in a specific area to dissolve mineral)

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6
Q

Active osteoclasts have a specialized border called

A

ruffle border

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7
Q

Ruffled border function

A

increase SA in resorption compartment

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8
Q

Lifespan of osteoclast

A

short - days

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9
Q

Osteoclasts are responsible for:

A
  1. bone resporption during normal bone growth
  2. removal of alveolar bone during tooth eruption
  3. resorption of primary teeth roots
  4. orthodontic movement bone removal
  5. Bone loss pathologies
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10
Q

Growth occurs at what point on a bone

A

epiphyseal plate

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11
Q

Transcription regulation:

A

NFATc1
C-fos
NfkB

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12
Q

NFATc1

A

master transcription factor

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13
Q

Growth Factor Regulation

A

Two factors produced by osteoblasts/cytes that are essential for OCL differentiation
RANKL and M-CSF

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14
Q

M-CSF

A

aka CSF 1 macrophage colony stimulating factor - promotes survival of osteoclast precursors

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15
Q

RANKL

A

receptor activator of NFkB ligand - member of TNF family - required for osteoclasts fusion and differentiation

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16
Q

OPG

A

osteoprotogerin - inhibitor of RANKL - decoy receptor

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17
Q

What do osteoclasts need to do?

A
  1. differentiate/fuse
  2. adhere to surface of bone
  3. produce acid
  4. produce protease
  5. Respond to factors to regulate itself
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18
Q

TRAP

A

enzyme - tartrate resistant acid Phosphatase

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19
Q

Receptors on osteoclasts (4)

A

RANK
C-fms
Calcitonin receptor
Integrin avB3

20
Q

Proton generators on osteoclasts

A

Carbonic Anhydrase II
Vacuolar-type ATPase

21
Q

Proteases on osteoclasts

A

Cathepsin K
MMP9, MMP13

22
Q

Osteoclasts attach via

A

avb3 integrins

23
Q

what forms the sealed zone

A

avB3 integrins

24
Q

CAII - generate _______ from CO2 and H2O and bicarbonate as a side product

A

protons

25
Q

Vacuolar Type ATPase function

A

pumps generated protons to resorption lacuna

26
Q

Cl- and HCO3- exchanger moves what?

A

bicarbonate excess product created by CAII

27
Q

Chloride channel in osteoclast function

A

maintain charge neutrality

28
Q

Cathepsin K

A

released into resporption lacuna to digest matrix proteins

29
Q

Impaired osteoclast Function leads to

A

osteopetrosis

30
Q

Osteopetrosis can be due to failure in two things:

A

impaired formation or funciton of osteoclasts

31
Q

Autosomal Dominant

A

adult benign - few symptoms

32
Q

Autosomal Recessive

A

infantile - malignant form, typically fatal if untreated

33
Q

Bones are abnormally _________ in osteopetrosis

A

dense and prone to fracture

34
Q

Osteopetrosis normally accompanied by

A

scoliosis, nerve compression, impaired marrow funciton, enlarged liver or spleen, infections, short stature

35
Q

Mutations in what 3 things can lead to osteoPETrosis

A

TCIRG1 (vacuolar APTase a-subunit) , CLCN7 (chloride channel) , Cathepskin K

36
Q

cathepsin K mutations are associated with

A

pychnodysostosis

37
Q

OsteoPORosis

A

Loss of bone mass, often associated with menopause or aging, affects men and women

38
Q

Osteoporosis BMD = patient with a BMD ___________ standard deviations from the average

A

greater than 2.5

39
Q

Osteoporosis _______ the risk of fractures

A

increases

40
Q

If bone formation cant keep up with bonen destruction:

A

we lose bone mass

41
Q

Anti-resorptive treatments

A

Amino bisphosponates, hormone replacement therapy, Selective Estrogen Receptor Modulators, Denosumab, Cathepsin K inhibitors

42
Q

Anabolic Agents

A

PTH-184, teriparitide, anti-sclerostin antibodies

43
Q

_____________ widely used for treatment of osteoporosis

A

oral bisphosphonates

44
Q

IV bisphosphanates are used for treatment of

A

myeolma/bone metastatic cancers

45
Q

______________ - non hydrolyzable analogs of pyrophosphates - inhibit mineralization similarly to PP

A

Bisphosphonates

46
Q

Bisphosphonates have a high affinity for

A

hydroxyapatite

47
Q

FINISH THIS SET SLIDE 27-on

A

Applied Biochem (13 decks)

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