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MSS > Bone Cell Biology > Flashcards

Bone Cell Biology Flashcards

1
Q

What is the function of bone?

A

infrastructure

bone marrow (5% body weight)

reservoir of Ca and phosphate

specialized CT: realize the bone is calcified ECM

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2
Q

WHat cells are involved in bone?

A

osteoblasts

osteocytes

osteoclasts

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3
Q

What are osteoclasts activated by? inhibited by?

A

osteoclasts are

activated by PTH (parathyroid) (to relase and increase Ca)

inhibited by calcitonin (thyroid)

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4
Q

How much of bone is inorganic matrix, and what makes it up?

A

70%

Ca and phosphorous= hydroxyapatite

99% of boy’s Ca is stored in bone

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5
Q

what makes up the organic matrix of bone?

A

30%

osteoid

  • type I collagen confers acid(eosin)ophilia
  • proteoglycans: less than in cartilage
  • glycoproteins: promote hydroxyapatitie
    • osteocalcin, a bone specific glycoprotein, is one agent that romotes mineralization
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6
Q

what is osteocalcin and what does it promote?

A

a bone-specific glycoprotein that promotes mineralization

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7
Q

Compare these following components between bone and hyaline cartilage:

  • mineral
  • water
  • collagen
  • neuronal and vascular strucutres
A
  • Mineral
    • bone: 70%
    • hyaline cartilage: none
  • Water
    • bone: 25%
    • hyaline cartilage: 75%
  • Collagen
    • bone: type I
    • hyaline cartilage: type II
  • Neuronl and vascular structures
    • bone: present
    • hyaline cartilage: none
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8
Q

what are osteoblasts?

A

specialized fibroblasts

  • bone morphogenic proteins (BMPs) and other growth factors induce differentiation from Mesenchymal Stem Cells (MSCs) into osteoblasts
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9
Q

Groups of osteoblasts make ________-

A

groups of osteoblasts make osteoid

  • osteoid is type I collagen and glycoproteins-single osteoblasts can’t do this
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10
Q

Bone formation is completed by ________

A

bone formation is completed by deposition of Ca in the osteoid

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11
Q

what is hydroxyapatite essential for?

A

weight bearing. without it, there is no weight bearing

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12
Q

WHat is the “bone master gene” and what does kncoking it out produce

A

the bone master gene is Runx2. knocking out Runx2 prevents bone development

**note Runx2 and osteocalcin are osteoblast specific

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13
Q

where are osteocytes located? Osteocytes comprise what percentage of bone cells?

A
  • occupy lacunae between lamellae of bone matrix, only one osteocyte per lacunae
  • 90% of bone cells
  • cytoplasmic “dendrites” penetrate the matrix and bind other osteocytes via gap junctions
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14
Q

What is the function of osteocytes and how long do they last?

A
  • mechano-sensation, therby regulating bone remodeling
  • secrete sclerostin, which inhibits Wnt signaling in osteoblasts, thereby stopping bone growth
  • osteocytes live a long time! half life is 25 years!!
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15
Q

What is the function of osteoclasts? what are they and how do they form? where do they live?

A
  • destroy bone matrix for remodeling and have ruffled borders that attach ECM, forming a microenvironment for bone resportion
  • multinuclear bc of development from macrophage like cells that fuse together
  • reside in hollowed-out areas of matric termed “Howship’s lacunae”
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16
Q

What is the significance of the ruffled borders of osteoclasts?

A

attach ECM, forming a microenvironment for bone resorption

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17
Q

WHat are osteoclasts regulated by?

A

hormones!!

  • Calcitonin (thyroid) inhibits osteoclasts
  • PTH (parathyroid) actiavtes osteoclasts
    • lysosomes-cathepsin K-microenvironment
    • Co2-H2CO3 (carbonic acid) - HCO3 (bicarb) + H- microenvironment optimized for bone resportion
    • basically, carbon dioxide becomes carbonic acid which becomes bicarb and H which is the appropriate environment for bone resportion
18
Q

What is this an image of?

A

Howships lacuna!

remember osteoclasts reside in howships lacuna

19
Q

Bone is lined by outer and inner layer of connective tissue respectively termed _____ and _______

A

Periosteum and endosteum!!

outer=periosteum

inner= endosteum

20
Q

Where are osteoblasts located?

A

periosteum, with small numbers in the endosteum

21
Q

where are the osteocytes located?

A

lacunae of the bony matrix, which lies between the periosteum and endosteum

22
Q

where are osteoclasts located?

A

most found attached to bony matrix on the endosteal side

23
Q

What is the difference between compact and spongy bone

A

compact aka cortical (80% of long bone) is dense with no cavitation

spongy aka cancellous aka trabecular bone (20% of long bone) is cavitated

24
Q

Flat bone vs long bone

A
  • flat (calvaria): 2 plates of compact bone surrounding diploe of spongy bone
  • long bones:
    • diaphysis (shaft): compact with spongy bone lining marrow
    • epiphyses (ends): caps of compact bone around spongy bone
25
Q

what is the unit of bone structure?

A

the osteon which is a cylinder with concentric lamellae

26
Q

lamellae have lacunae that do what 2 things?

A

lamellae have lacunae that

  1. harbor osteocytes
  2. are connected via canaliculi
27
Q

what does the innermost lamella surround?

A

Haversian canal

28
Q

What are the 2 ways by which bones can develop from primary bone to secondary bone (lamellar, mature)?

A
  1. intramembranous
    1. osteoblasts deposit osteoid onto a loos eframework of reticular connective tissue (not really a membrane)
  2. endochondral
    1. osteoblasts deposit osteoid onto cartilage
29
Q

During endochondral development bone forms on what?

A

hyaline cartilage

30
Q

what occurs at the diaphysis during endochondral development? how about at the epiphyses?

A
  • diaphysis: osteoblasts invade calcified cartilage and secrete osteoid which leads to ossification
  • epiphyses: same process, articular cartilage remains at the ends of the bone and epiphyseal plate cartilages remain v diaphyses and epiphyses, for growth in length
31
Q

How do long bones get long?

A
  • sex steroid hormones—- pituitary—– growth hormone (GH; somatotropin) —- liver—-IGF1—-epiphyseal plate
  • zone of cartilage proliferation is activated by IGF-1
  • zone of cartilage hypertrophy is where 20% of fractures occur
  • zone of cartilage calcification (collagen X not collagen II)
  • zone of ossification: eosinophilia due to deposition of collagen I by osteoblasts
32
Q

How do fractures repair?

A
  1. macrphages remove debris
  2. fibroblasts and chrondroblasts secrete a fibrocatilaginous callus
  3. osteoblasts replace fibrocartilaginous callus with bony callus
  4. primary bone is repaced by lamellar secondary bone
33
Q

how do we get a new skeleton every 10 years!

A

osteoclasts excavate bone which is then replaced by actiavted osteoblasts

34
Q

what is osteopetrosis? what is osteoporosis?

A
  • osteopetrosis: dense heavy bone; osteoclasts lack ruffled border
  • psteoporosis: resorption by osteoclasts outpaces osteogenesis leading to hollow fragile bones
35
Q

whats is osteoporosis? who gets it? what are they at risk for/ how do we prevent that?

therapeutic targets?

A
  • 28 million americans with 2/3 women. postmenopausal lose 2% bone mass annually
  • treatable, therapeutic targets are osteoclasts and osteoblasts
  • at risk for breaks at wrist, hip and spine
    • prevention:
      • dietary Ca, vitamin D (improves absorption of Ca)
      • weight bearing exercise
        *
36
Q

WHat is the screening test for osteoporosis?

A
  • bone mineral density (BMD, grams/cm2)
    • compare BMD with “young-normal” subjects
    • T score= # of standard deviations below the young normal mean (note it declines with age)
37
Q

how are osteoclasts produced?

A
  • stromal cells in the bone marrow are induced by PTH to secrete 3 factors RANKL, OPG, and M-CSF. these act on monocytes
  • M-CSF induces monocyte/macrophage proliferation
  • RANKL (receptor for activator of nuclear factor kB ligand) induces differentiation into osteoclasts
  • OPG= osteoprotegerin antagoizes RANK-L by binding to its receptor; hence OPG inhibits osteoclast production
38
Q

Osteoblasts are inhibited by what? and induced by what?

A

osteoblasts:

  • inhibited by leptin (obesity> risk for osteoporosis)
  • induced by BMP
  • induce by PTH
39
Q

osteoclasts are inhibited by what and induced by what?

A

osteoclasts

  • inhibited by calcitonin, osteoprotegerin
  • induced by RANK-L
  • induced by PTH
40
Q

why is it weird that PTH induces osteoblasts and osteoclasts?

A

bc they are “opposing” bone cells

41
Q

What are the anabolic drugs to treat osteoporosis?

A
  • PTH 1-34 teriparatide= Pro-osteoblast
    • resolution of PTH paradox: “spikes” of PTH level, as attained by injection, favor osteoblast production, whereas constant PTH levels favor osteoclasts
  • Anti-resorptive drugs= antiosteoclast
    • SERMs (selective estrogen receptor modulators) raloxifene
    • biphosphates: ibandronate (Boniva)
    • mAbs (Denosumab) bind RANKL
  • In pipelineL drugs with more specificty
    • osteoclast inhibitor
    • drugs that inhibit bidning osteoclasts to matrix
    • anabolic agents such as Runx2

MSS (26 decks)

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