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MSK Test 1 > LEC-9 Regulation of Bone > Flashcards

LEC-9 Regulation of Bone Flashcards

1
Q

A(n) _______________ is the rudimentary basis of a particular organ or other part of the body, especially in an embryo.

A

Anlage

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2
Q

___________ is the growth factor responsible for vascularization of bone during endochondral ossification.

A

VEGF (Vascular endothelial growth factor)

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3
Q

What is the first step of intramembranous ossification?

A
  1. An ossification center appears in the fibrous connective tissue membrane.
    * Specially selected central mesenchymal cells cluster and differentiate into osteoblasts, forming an ossification center.
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4
Q

What is the second step of intramembranous ossification?

A
  1. Bone matrix is secreted into the surrounding fibrous connective tissue membrane.
  • Osteoblasts begin to secrete osteoid, which becomes mineralized within a few days time.
  • Osteoblasts trapped within the membrane become osteocytes.
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5
Q

What is the third step of intramembranous ossification?

A
  1. Woven bone and periosteum form.
  • Accumulating osteoid is laid down between embryonic blood vessels which forms a random network. The result is a network of trabeculae.
  • Vascularized mesenchyme condenses on the external face of the woven bone and becomes the periosteum.
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6
Q

What is the fourth step of intramembranous ossification?

A
  1. Bone collar of compact bone forms and red marrow appears.
  • Trabeculae just deep to the periosteum thicken, forming a woven bone collar that is later replaced with mature lamellar bone.
  • Spongy bone (diploë), consisting of distinct trabeculae, persists internally and its vascular tissue becomes red marrow.
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7
Q

What are the stages of endochondral ossification?

A
  1. Formation of bony collar (through intramembranous ossification)
  2. Cavitation of hyaline cartilage model within bone collar
  3. Invasion of internal cavities by periosteal bud and spongy bone formation
  4. Formation of medullary cavity, appearance of secondary ossification centers in epiphyses
  5. Ossification of epiphyses with hyaline cartilage remaining only in epiphyseal plates
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8
Q

The _______ family of signal transduction pathways and proteins consists of small, cysteine-rich secreted glycoproteins that bind to receptors of the LRP and Frizzled family. It is important during development and continues to remain important during post-natal life.

A

Wnt

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9
Q

(T/F) The Wnt pathway is currently a therapeutic target for bone catabolism.

A

False. The Wnt pathway is currently a therapeutic target for bone anabolism.

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10
Q

The ______ family of proteins serves as a cellular membrane-bound receptor for Wnt, but are related to the LDL family of membrane receptors. Mutations in this particular family of proteins may lead to osteopetrosis.

A

LRP

  • Lipoprotein Receptor-related Protein
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11
Q

Once Wnt is bound to its membrane receptors, LRP5/6 and Frizzled, the nuclear transcription factor known as ______________ signals for the transcription of osteoblastic genes.

A

β-catenin

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12
Q

What is the general layout of cells within the epiphyseal plate, or growth plate?

A

Image

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13
Q

Label the following histological image of a growth plate.

A

Image

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14
Q

Bone produces type (I/II/III/IV/X) collagen.

A

Type I

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15
Q

Proliferating cartilage produces type (I/II/III/IV/X) collagen.

A

Type II

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16
Q

A hypertrophying chondrocyte produces type (I/II/III/IV/X) collagen.

A

Type X

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17
Q

(Sox/Runx2) and (Osx/IHH) drive mesenchymal cells toward chondrocyte differentiation.

A

Sox and IHH (Indian Hedgehog)

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18
Q

(Sox/Runx2) and (Osx/IHH) drive mesenchymal cells toward bone differentiation.

A

Runx2 and Osx

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19
Q

Mutations of the Runx2 gene in humans that results in heterozygosity of the gene causes ___________________, a disorder in which there is delayed ossification of midline structures such as the collarbone. Individuals are able to bring their shoulders abnormally close to their midline and suffer from other skeletal defects.

A

Cleidocranial dysplasia

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20
Q

What are the primary malformations seen in cleidocranial dysplasia, a disease caused by heterozygosity of the Runx2 gene?

A
  • Complete or partial absence of clavicle
  • Delayed ossification of fontanelles
  • Premature closing of coronal suture
  • Protruding jaw and brow
  • High arched palate or possible cleft palate
  • Short stature
  • Scoliosis
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21
Q

Osx acts (upstream/downstream) of Runx2.

A

Downstream

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22
Q

______________ is secreted from perichondrial cells and chondrocytes nearest to the ends of long bones. This protein acts on the receptors of proliferating chondrocytes to continue stimulation of proliferation and to delay the production of IHH. When the source of this protein moves a sufficient distance away from a chondrocyte, IHH is then produced.

A

PTHrP

  • Parathyroid Hormone-related protein
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23
Q

____________ is secreted from chondrocytes no longer under the influence of PTHrP. This protein acts on its chondrocyte receptors to increase proliferation, stimulate production at PTHrP at the ends of long bones, and influences perichondrial cells to become osteoblasts, triggering formation of the bone collar.

A

IHH

  • Indian Hedgehog
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24
Q

FGFR-(1/3) mediates the negative and inhibitory effects of FGF ligands, such as a decrease in chondrocyte proliferation and a decrease in IHH production.

A

FGFR-3

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25
Q

FGFR-(1/3) mediates the positive and stimulatory effects of FGF ligands, such as an increase in the differentiation of hypertrophic chondrocytes into terminally differentiated chondrocytes that produce osteopontin and other characteristic markers.

A

FGFR-1

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26
Q

Achondroplasia, or dwarfism, may be linked to activating mutations within the gene or protein ___________.

A

FGFR-3

  • Fibroblast Growth Factor Receptor 3
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27
Q

Achondroplasia is linked to (activating/deactivating) mutations within FGFR-3.

A

Activating

28
Q

Achondroplasia and the accompanying defect in FGFR-3 negatively influence (endochondral/intramembranous) ossification.

A

Endochondral ossification

29
Q

The main dysfunction in achondroplasia is the (overstimulation/overinhibition) of the proliferative zone in long bones due to FGFR-3 mutations.

A

Overinhibition

30
Q

What occurs during the bone remodeling cycle?

A

Image

31
Q

(Osteoclasts/Osteoblasts) are cells that produce osteoid, or bone matrix. They are derived from a mesenchymal cell lineage, produce type I collagen, and express parathyroid hormone receptor. They are also responsible for the production of osteocalcin and bone sialoprotein, extracellular matrix proteins specific to bone. These cells line the surface of bone and follow cells responsible for bone resorption in cutting cones.

A

Osteoblasts

32
Q

P1CP and P1NP are propeptides involved in type I collagen (degradation/synthesis).

A

Synthesis

33
Q

ICTP and CTX are fragments involved in type I collagen (degradation/synthesis).

A

Degradation

34
Q

What are the growth factors and regulators involved in bone differentiation?

A
  • Wnt
  • BMP
  • TGF-β
  • PTH
  • Glucocorticoids
  • Vitamin D
  • IGF1
  • PGE2
35
Q

What are the matrix proteins involved in bone differentiation?

A
  • Collagen I
  • Osteopontin
  • Alkaline phosphatase
  • Bone sialoprotein
  • Osteocalcin
36
Q

(T/F) Mechanical loading stimulates mesenchymal differentiation towards bone and bone growth.

A

True.

37
Q

An activating mutation in the LRP family of membrane proteins will result in (osteoporosis/osteopetrosis).

A

Osteopetrosis

38
Q

(Sclerostin/DKK1) inhibits Wnt signaling by the formation of complexes with LRP5/6 and Kremen.

A

DKK1

39
Q

(Sclerostin/DKK1) inhibits Wnt signaling by binding to LRP5/6.

A

Sclerostin (SOST)

40
Q

Sclerostin is secreted by (osteoblasts/osteocytes/osteoclasts) in order to stop osteoblastic bone growth.

A

Osteocytes

41
Q

Sclerostin (inhibits/promotes) osteoblast apoptosis.

A

Promotes

42
Q

Point mutations that cause the inactivation of SOST result in ______________.

A

Sclerosteosis (bone overgrowth)

43
Q

Sustained administration of PTH causes a(n) (increase/decrease) in bone mineral density (BMD).

A

Decrease

44
Q

Intermittent administration of PTH causes a(n) (increase/decrease) in bone mineral density (BMD).

A

Increase

45
Q

The anabolic and recombinant form of PTH, h PTH1-34, is available clinically as a drug named __________.

A

Forteo

46
Q

What are common targets for bone anabolic therapy?

A
  • Teriparatide (PTH)
  • PYK2 Inhibitors (PYK2 inhibits Wnt and bone differentiation)
  • Sclerostin antibodies
  • DKK1 antibodies
  • Statins
  • Strontium
47
Q

Describe osteoclast differentiation.

A

Image

48
Q

Osteoclasts (are/are not) mesenchymal in origin.

A

Are NOT

49
Q

____________ is produced by osteoblasts and is a known survival factor for osteoclast progenitor cells.

A

m-CSF (Macrophage Colony Stimulating Factor)

50
Q

__________ is a protein produced by and expressed on the surface of osteoblasts that, once bound by its receptor counterpart on osteoclast precursors, signals for the production of NF-κB and c-fos, key differentiation proteins within the osteoclast precursor.

A

RANKL

51
Q

The receptor counterpart to RANKL expressed on the surface of osteoclasts is ____________.

A

RANK

52
Q

Once RANKL on the osteoblast is bound to RANK on the osteoclast, ____________ and ____________ are produced within the osteoclast precursor to promote differentiation.

A

NF-κB and c-fos

53
Q

(T/F) Either m-CSF or the RANK/RANKL complex alone is sufficient to signal for osteoclast precursor differentiation.

A

False. You need both m-CSF and the RANK/RANKL complex to complete osteoclast precursor differentiation.

54
Q

________________ are recruited to become osteoclast progenitors since mesenchymal cells are not used for osteoclast development.

A

Hematopoietic stem cells

55
Q

________________ is an osteoclast regulation protein that inhibits the formation of the RANK/RANKL complex by serving as a decoy receptor for RANKL.

A

Osteoprotegerin (OPG)

56
Q

_______________ are steroid hormones within the body that inhibit osteoblast differentiation and enhance osteoclast differentiation.

A

Glucocorticoids

  • Stress eats bones
57
Q

_______________ is a hormone within the body that directly causes apoptosis of osteoclasts and increases production of TGF-β from T cells, inhibiting osteoclastogenesis.

A

Estrogen

58
Q

What are the relative relationships and processes involved in bone formation and bone resorption?

A

Image

59
Q

(Osteoporosis/Osteopetrosis/Osteomalacia/Paget’s disease) is the increased bone mass associated with unopposed bone formation. Occurs from a defect in bone resorption.

A

Osteopetrosis

60
Q

(Osteoporosis/Osteopetrosis/Osteomalacia/Paget’s disease) is the localized disorder of bone remodeling. It is caused by an increase in osteoblast and osteoclast activity and high alkaline phosphatase.

A

Paget’s disease

61
Q

(Osteoporosis/Osteopetrosis/Osteomalacia/Paget’s disease) is the high turnover of bone. It is caused by the increased resorption of bone over increased formation, resulting in decreased bone mass and non-traumatic fractures (usually in post-menopausal women).

A

Osteoporosis

62
Q

(Osteoporosis/Osteopetrosis/Osteomalacia/Paget’s disease) is the low turnover and inadequate mineralization of bone. This is most often caused by a defect in bone mineralization that may result from an underlying insufficiency in calcium or vitamin D.

A

Osteomalacia

63
Q

_____________ bone is most vulnerable during osteoporosis.

A

Trabecular or cancellous or spongy

64
Q

The main symptom of osteomalacia is _________________.

A

Pain when weight is applied to bone

65
Q

_________________ is a disease of improper bone formation due to a type I collagen defect.

A

Osteogenesis Imperfecta

66
Q

The primary treatment for osteogenesis imperfecta is _________________.

A

Bisphosphonates (inhibits bone digestion by promoting osteoclast apoptosis)

67
Q

What genetic defects are responsible for osteogenesis imperfecta?

A
  • COL1A1
  • COL1A2

MSK Test 1 (11 decks)

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