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FPP_MSS > Bone Cell Biology - Lough > Flashcards

Bone Cell Biology - Lough Flashcards

1
Q

What functions are served by bones?

A

Structural support

Housing of bone marrow

Calcium/phosphate reservoir

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2
Q

What percentage of bone is inorganic (by mass)?

What mineral largely comprises it?

A

70%

Hydroxyapatite

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3
Q

What name refers to the organic component of bone matrix? Why does it stain red?

A

Osteoid

Type I collagen is Acidophilic. (remember, bONE has type ONE collagen)

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4
Q

What two genes are unique to osteoblasts, and what are their functions?

A

Cbfa-1/Runx2: “Master” transcription factor (absence = dysostosis).

Osteocalcin: Matrix glycoprotein that facilitates Ca2+ deposition.

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5
Q

What are BMPs?

A

Bone Morphogenetic Proteins, members of the TGFβ superfamily which activate osteoblast differentiation.

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6
Q

How long-lived are osteocytes? Describe their location/distribution.

A

25yr half-life

They occupy lacunae between lamellae within osteons. They communicate via canaliculi (house cytoplastic processes, gap junctions)

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7
Q

How are osteoclasts formed? Describe their structure and distribution.

A

Formed from macrophages that fuse together (multinuclear!)

Found in “Howship’s Lacunae”, with ruffled borders forming a microenvironment within the matrix.

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8
Q

What is the effect of PTH on osteoclasts? Describe how this can impact serum calcium levels.

A

PTH activates lysosomes, which dump H+ and cathepsin-K to resorb the bony matrix. This results in increases in serum calcium.

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9
Q

Which bony cells are found in the periosteum? The endosteum?

A

Osteoblasts are found in both. Osteoclasts are mostly found in the endosteum. Osteocytes are buried in lacunae within the bone matrix.

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10
Q

Describe the distribution of compact vs spongy bones in flat and long bones.

A

In flat bones, spongy bone is surrounded by plates of compact bone.

In long bones, the same is true as a cylinder (diaphysis), with caps of compact bone at either end (epiphyses).

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11
Q

What is the name for a canal that travels perpendicular to the length of the bone?

A

Volkmann’s canal.

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12
Q

Distinguish between endochondral ossification at the diaphysis and epiphyses of a long bone.

A

At the diaphysis, osteoblasts invade calcified cartilage and lay down osteoid. Bone laid down under periosteum = increase in diameter.

At the epiphyses, chondrocytes proliferate and produce cartilaginous matrix. This is replaced with osteoid by osteoblasts, resulting in an increase in length.

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13
Q

Describe the pathway by which sex hormones (say, during puberty) can promote increase in bone length.

A

Sex hormones act on the pituitary to promote growth factor, which activate the liver to produce somatomedin/IGF-I, which stimulates chondrocytes.

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14
Q

Which types of collagen can be found at the site of endochondral ossification?

A

Collagen I (from osteoblasts)

Collagen II (from chondrocytes)

Collagen X (calcified; from chondrocytes)

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15
Q

Summarize the process of fracture repair.

A
  1. Macrophages remove debris.
  2. Chondrocytes form a hyaline cartilage callus.
  3. Osteoblasts replace it with a bony callus.
  4. The primary bone is replaced by lamellar, secondary bone.
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16
Q

Distinguish between the pathophysiologie of Osteopetrosis, Osteoporosis, and Paget’s Disease.

A

Osteopetrosis results from deficient osteoclast activity.

Osteoporosis results from excessive osteoclast activity.

Paget’s disease results from overactive osteoblasts AND osteoclasts.

17
Q

Osteoporosis

Where are fractures most common?

What are some simple preventative measures?

How is it monitored/screened?

A

Osteoporosis

At the wrist, hip, and spine.

Treat with Ca2+ & Vitamin D supplements, and resistance exercise.

Screen with bone mineral density assays (yields a “T-score”).

18
Q

What signals are required for osteoclast production?

What role does OPG play here?

A

M-CSF to induce macrophage proliferation, and RANK-L on stromal cells to trigger their differentiation to osteoclasts.

OPG or osteoprotegerin, inhibits RANK (the receptor).

19
Q

Summarize hormonal control of osteoblast and osteoclast activity.

A

Osteoblasts are inhibited by leptin, but induced by BMP and intermittent PTH.

Osteoclasts are inhibited by calcitonin and OPG, but induced by RANK-L or continuous PTH.

20
Q

Describe some drugs used (or planned) to treat osteoporosis.

A

PTH 1-34 (“Forteo”) given in spikes to promote osteoblast activity.

SERMs to replace deficient estrogen signaling.

Bisphosphonates (eg Boniva)

Calcitonin

(experimental) OPG, CBFA-1, or adhesion inhibitors.

21
Q

What are the (3) chief components of the osteoid?

A
  1. Collagen I
  2. proteoglycans
  3. osteocalcin (glycoprotein) -> promotes hydroxyapatite formation
22
Q

What type of collagen is found in hyaline cartilage?

A

Type II collagen

23
Q

What type of collagen is found in bone?

A

Type I collagen

24
Q

What is osteomalacia?

A

Softening of the bone tissue caused by deficient mineralization

25
Q

What is Rickets?

A

Pediatric osteomalacia

26
Q

What disease resulting in excessive loss of bone mass features hypernucleated osteoclasts?

A

Paget’s Disease

27
Q

Name the lysosomal enzyme released by osteoclasts that is responsible for the breakdown of collagen in bone resorption?

A

Cathepsin-K

28
Q

Name (2) synonyms for spongy bone

A

Cancellous

Trabecular

29
Q

Name the canal type that generally runs parallel to the long axis of bone

A

Haversian canal

30
Q

Primary (woven) bone is primarily found in what processes?

A

Fetal development

Repair

31
Q

Name and describe the (5) zones of the epiphyseal plate

A
  1. Reserve cartilage
  2. Zone of proliferation (induced by IGF-I)
  3. Zone of hypertrophy: hollowed out area responsible for 20% of fractures
  4. Zone of calcification: calcified cartilage zone with collagen X (basophilic)
  5. Zone of ossification: deposition of collagen I by osteoblasts (eosinophilic)
32
Q

Describe the process of osteoclast production

A

Stromal cells in bone marrow are induced by PTH to secrete 3 factors that regulate osteoclast formation:

  1. M-CSF (macrophage colony stimulating factor): induces macrophage proliferation
  2. RANK-L (receptor for activator of nuclear factor-kb ligand): induces macrophage differentiation/fusion into osteoclasts
  3. OPG (osteoprotegerin): RANK-L receptor antagonist (i.e. antagonizes macrophage differentiation)
33
Q

What is a T-score (for bones)?

A

Expression of bone marrow density (BMD): the T-score is the number of standard deviations below healthy normal BMD

34
Q

What is α5ß3?

A

A protein expressed by osteoclasts along the margins of the ruffled border that helps seal and form the Howship’s lacuna (resorptive pit microenvironment)

May be a promising drug target in the treatment of osteoporosis

35
Q

Drugs: describe teriparatide (PTH 1-34)

A

Produces spikes of PTH level, favoring osteoblast production

Used in clinical management of osteoporosis, especially at T-score < -2.5 where anti-resorptive drugs become ineffective

36
Q

Name (3) anti-resorptive (anti-osteoclast) drugs used in the treatment of osteoporosis

A

SERMs (selective estrogen receptor modulators) -> raloxifene

Bisphosphonates: ibrandronate (Boniva)

calcitonin

37
Q

What is ibandronate?

A

bisphosphonate drug, used as an anti-resorptive (anti-osteoclast) in the treatment of osteoporosis

Marketing name: Boniva

38
Q

What is raloxifene?

A

A SERM (selective estrogen receptor modulator) drug used as an anti-resorptive (anti-osteoclast) in the treatment of osteoporosis

39
Q

Name an anabolic drug that produces PTH spikes designed to promote osteoblast production in bone

A

teriparatide (PTH 1-34)

Marketing name: Forteo

FPP_MSS (30 decks)

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