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CELL 302 > Lecture C8 + C11 > Flashcards

Lecture C8 + C11 Flashcards

1
Q

3 functions of bone

A

-solid support for body, protects vital organs
-bone marrow is site of blood cell production
0reservoir of calcium phosphate and other ions

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2
Q

3 cells of bone

A

-osteoblats
-osteocytes
-osteoclasts

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3
Q

osteoblasts do what?

A

-secrete matrix that hardens by calcification, trapping the osteocytes

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4
Q

osteoblats arise from _____

A

-osteogenic cells

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5
Q

osteocytes do what?

A

maintain the calcified matrix and receive nutrients from microvasculature

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6
Q

osteoclasts are _____ and do what?

A

monocytes-derived giant multinucleated cells involved in removing calcified bone matrix and remodelling bone tissue.

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7
Q

osteoblasts? osteoclasts?

A

-build (bone markers)
-chew (bone breakers)

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8
Q

osteoblasts come from ______. osteoclasts come from _____. osteocytes also can come from ______

A

-mesenchymal stem cells
-hematopoietic stem cells
-mesenchymal stem cells

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9
Q

Osteoclasts are large multinucleated cells that are derived by the fusion in bone of _______

A

-several blood-derived monocytes

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10
Q

Osteoclasts are continually ______ while osteoblasts are continually _______. The ongoing balance between osteoblasts and osteoclasts is responsible for the constant but subtle _____

A

-breaking down old bone
-forming new bone
-reshaping of bone

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11
Q

Osteoblasts are activated by _____ produce ________ and other factors that regulate the formation and activity of osteoclasts.

A

-parathyroid hormone
-macrophage colony-stimulating factor (M-CSF), receptor activator of nuclear factor κB ligand (RANKL)

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12
Q

Osteoclasts: M-CSF is required for ______ while ______ itself is controlled by RANKL.

A

-precursor cell survival
-differentiation

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13
Q

Osteoclast progenitors, express ____, the receptor for M-CSF. Upon M-CSF binding to the receptor, these cells express ______, which is activated by RANKL.

A

-cFMS
-RANK receptor

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14
Q

Binding of RANKL to RANK, in cooperation with other signals, induce ______. Osteoclast precursors fuse to form ______. Continuous signaling by RANK induces their _____

A

-differentiation of the progenitor cells to osteoclast precursors.
-multinucleated osteoclasts
-activation to mature, bone resorbing osteoclasts

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15
Q

RANK-RANKL signaling results in a _____. Chemotaxis brings cells towards each other, which is mediated by ______. Cell–cell adhesion is partly mediated by _____, and subsequent cytoskeletal rearrangements are regulated by _____. The ____ cytoskeleton organize to form podosomes, which are ______

A

-fusion-competent status
- binding of C-C motif chemokine ligand 2 (CCL2) to its receptor (CCR2)
-E-cadherin and integrins
-RAC1
-actin
-specialized macrophage adhesion structures

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16
Q

Podosomes exhibit two distinct features: ________. Podosomes are highly interconnected through a _____. The formation of ____ rings
by podosomes forms the _____.

A

-an actin core and an adhesive ring complex, containing integrins
and integrin-associated proteins
-dense network of filamentous actin (F-actin).
-actin
-sealing zones

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17
Q

Membrane fusion, and thus the formation of osteoclasts by cell-cell fusion, is mediated by _____

A

-dendrocyte expressed seven transmembrane protein (DC-STAMP)

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18
Q

Osteoclasts secretes many ____ into the ECM that function in bone remodeling.

A

enzymes (proteases that digest collagen)

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19
Q

In an active osteoclast, the membrane domain that contacts the bone forms a ____ that binds the cell tightly to the bone matrix and surrounds an area with many surface projections, called _____. This circumferential sealing zone allows the formation of a _____ between the osteoclast and the matrix in which bone resorption occurs.

A

-circular sealing zone
-the ruffled border
-specialized microenvironment

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20
Q

The sealed space between the osteoclasts and the matrix is _____ by proton pumps. The ruffled border receives _____. Acidification of the sealed space promotes ______ from bone. Together with protein hydrolases that degrades the ECM, this leads to _____. The breakdown products of collagen fibers and other polypeptides are ____ by the osteoclast and further _____, while Ca and other ions are released _____.

A

-acidified to ~pH 4.5
-secreted matrix metalloproteases and other hydrolytic enzymes
-dissolution of CaPO4 complexes
-localized matrix resorption
-endocytosed
-degraded in lysosomes
-directly and taken up by the blood

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21
Q

Pit- and trench-forming osteoclasts

A

pit: osteoclasts sits directly on bone
trench: osteoclasts ruffled border on bone surface sideways

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22
Q

trench osteoclast more common in ____. pit?

A

-men
-women

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23
Q

_____ is released from the bone matrix and activated during osteoclast- mediated bone resorption, ____.

A

-Transforming growth factor beta (TGF-β1)
-creating a gradient

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24
Q

Synthesis and secretion of TGF-β

A

(1) TGF-β is synthesized as a precursor protein.
(2) Two TGF-β precursor proteins dimerize through disulfide bridges.
(3) TGF-β-dimer precursor is cleaved by furin to yield the small latent TGF-β complex, that contains latency-associated peptide (LAP) and mature TGF-β peptide connected by noncovalent bonds.
(4) The large latent complex is formed by covalent linking between small latent complex and latent TGF-β binding protein (LTBP), then secreted and incorporated into extracellular matrix.

25
Q

The LTBP (which is covalently linked to ______) is covalently cross-linked to _____. Osteoclasts can generate an acidic environment ideal for the activation of _____ richly deposited in the bone matrix. Osteoclasts can also activate latent TGF-β by _____, leading to the proteolytic cleavage of ____ and enrichment of ____ within the immediate environment of the bone resorption site.

A

-small latent TGF-β complex
-extracellular matrix, inactivated
-latent TGF-β
-secretion of proteases
-LTBP1
-active TGF-β

26
Q

Binding of active TGF-β with the _____ leads to the phosphorylation and recruitment of ____ into a heteromeric receptor complexes. The serine/threonine kinase activity of the activated complex phosphorylates _____ that both bind to ___ and translocate into the nucleus to enhance gene transcription by _____

A

-TGF-β receptor type II
-TGF-β receptor type I
-Smad2 and Smad3
-Smad4
-cooperating with DNA transcription factors

27
Q

Mesenchymal stem cells (MSCs) are activated by ___. They migrate to bone-resorptive sites and differentiate into ____.

A

-TGFβ1
-osteoblasts

28
Q

Bone remodeling sites are coupled with ______

A

-bone resorption and formation.

29
Q

Osteoblast progenitors express the transcription factor ______, a key player in the osteogenesis process.

A

-runt related transcription factor 2 (RUNX2)

30
Q

Osteoblasts are _____ specialized for the active
secretion of ECM. These cells have a relatively short-lifespan,
estimated at _____.

A

-polarized cuboidal cells
-3 months in human bones (either die or become osteocytes)

31
Q

Osteoblasts produce new bone called “____” which is made of bone collagen and other proteins. Then they control _____. Formation of
mineralized ECM results in the _____ that
forms bone.

A

-osteoid
-calcium and mineral deposition
-hard but lightweight material

32
Q

Osteocytes are derived from terminally differentiated ______. They are the most abundant cells in bone, composing ____ of all bone
cells in an adult. Once the bone mineralizes, the osteocytes are trapped there and form _____ . Osteocytes can survive throughout _____

A

-osteoblasts
-90–95%
-an extensive network with each other, with osteoblasts, and with the
lining cells on the bone surface
-the life of an individual

33
Q

Osteocytes descr.

A

have a small cell body and show numerous long, dendritic-like cytoplasmic prolongations that form a canalicular system inside bone

34
Q

During the transition from osteoblasts to osteocytes, the cells extend many _____ which also become surrounded by calcifying matrix

A
  • long dendritic processes
35
Q

Osteocytes serve as ____ detecting the mechanical load on the bone as well as stress - or fatigue -induced microdamage and to trigger ______

A

-mechanosensors
-remedial activity in osteoblasts and osteoclasts

36
Q

Osteoblasts that do not undergo apoptosis or differentiate to
osteocytes become _____.

A

-bone lining cells

37
Q

The bone lining cells then play a crucial role bone remodeling by communicating _____ and promoting differentiation of _____

A

-through gap junctions with osteocytes deep in the bone matrix
-hematopoietic stem cells into osteoclasts.

38
Q

The bone lining cells are responsible for ______ by removing _____ through the use of _____

A

-preparing the surface of the bone for remodeling
-nonmineralized collagen fibrils
-matrix metalloproteinases

39
Q

Duchenne muscular dystrophy (DMD) is what?

A

genetic disorder characterized by progressive muscle degeneration and weakness.

40
Q

DMD symptom onset is in ____ and the disease primarily affects ______ because _____

A

-early childhood between ages 2-3
-boys
-gene affected in on X chr

41
Q

DMD is caused by mutations in ____ (encoding _____) that prevent the production of the _____.

A

-DMD gene (largest gene)
-dystrophin
-muscle isoform of dystrophin

42
Q

DMD gene is located on _____. DMD inheritance pattern? passed on by _____

A

-X chromosome
-X-linked recessive
-carrier mother (unaffected)

43
Q

DMD in females?

A

rare; limited to females with Turner syndrome (X0) -only one X chr

44
Q

Dystrophin functions in muscle as a ______. Dystrophin is a component of the _____, which anchors the cytoskeleton to the ______ and stabilizes the ______ in response to contractions. Due to the modular structure of the dystrophin protein domains, ______ of dystrophin can retain function.

A

-mechanical link to tether the actin cytoskeleton to the inner surface of the sarcolemma
-dystrophin-glycoprotein complex (DGC)
-extracellular matrix
-muscle membrane
-internally truncated forms

45
Q

Dystrophin deficiency results in the disassembly of the ______ and in loss of the interaction between ______.

A

-dystrophin-glycoprotein complex (DGC)
-F-actin and the extracellular matrix

46
Q

Antisense oligonucelotides (AON) do what?

A

-promote exon skipping
-promote exon exclusion
-block translation

47
Q

Epidermolysis bullosa (EB) is an incurable group of rare genetic diseases characterized by _____ and ______, inducible by minimal trauma.

A

-mucocutaneous fragility
-blister formation

48
Q

Patients with EB can be _____; at the extreme end of the phenotypic spectrum, the disease can become ______.

A

-mildly to severely affected
-disabling or fatal

49
Q

Treatment of EB is _______; no available treatment can resolve the disease or its manifestations.

A

-symptomatic

50
Q

genes implicated in EB

A

-16 genes encoding proteins influencing cellular integrity and adhesion (laminins, integrins, collagens)

51
Q

Mammalian skin consists of the _____ and _____, separated by a _______. The comprises ______ that anchor the epidermis to the dermis.

A

-epidermis
-dermis
-basement membrane
-extracellular matrix macromolecules

52
Q

_______ of the intracellular cytoskeleton network attach to hemidesmosome plaques on the ______ of keratinocytes. Hemidesmosomes are linked to the underlying _____ via thread-like ______.

A

-Intermediate filaments
-basal plasma membranes
-lamina densa
-anchoring filaments

53
Q

______ deficiency causes continuous skin blistering; healed with ____. Patients with mutations in ____, the gene that codes for collagen VII. Herpes simplex virus was engineered to deliver normal ____ genes. The gene therapy was then incorporated into a ____ so it could be applied to the skin.

A

-LAM5-β3
-skin graft epidermal sheets expressing normal LAM5-β3
-COL7A
-COL7A1
-gel

54
Q

Attention-deficit hyperactivity disorder (ADHD) is a clinically heterogeneous neurobiological disorder of _______, affecting 5–7% of children worldwide.
ADHD is one of the most common _______ of childhood.
ADHD may occur either as an _______ with other neurological, psychiatric, and neurodevelopmental disorders.

A

-inattention, impulsivity, and hyperactivity
-neurodevelopmental disorders
-isolated condition or as comorbidity

55
Q

Dopaminergic neurons are primarily located respectively in the______ and control various functions.
______ contribute to the symptoms of inattention, hyperactivity, and impulsiveness in attention-deficit hyperactivity disorder.

A

-midbrain
-Anomalies in dopamine levels

56
Q

The most widely used medications of ADHD are two psychostimulants, ______

A

methylphenidate (MPH) and the amphetamines (AMP)

57
Q

methylphenidate (MPH) do what?

A

binds to NET and DAT, inhibiting the reuptake of norepinephrine and dopamine.

58
Q

amphetamines (AMP) do what? (3)

A
  • transported by the monoamine transporters DAT and NET, thus competing with those neurotransmitters (dopamine/norepinephrine)
    and decreasing their reuptake in the synapse
    -cause trace amine-associated receptor 1 (TAAR1) to phosphorylate DAT. The phosphorylated DAT is either internalized into the presynaptic neuron and ceases transport or inverses the efflux of dopamine
    -enter the presynaptic vesicle and cause efflux of neurotransmitters off the vesicle, which in turn augments the efflux towards the synapse.
59
Q

DAT is _____. NET is ____

A

-dopamine transporter into cells
-norepinephrine transporter

CELL 302 (18 decks)

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