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92 Cards in this Set
- Front
- Back
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What are the two types of cell death?
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necrosis or apoptosis
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What are the two types of cell death?
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necrosis or apoptosis
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What are the three causes of apoptosis?
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1. physiologic (programmed)
2. pathologic (e.g. removal of damaged tissue or disease like Parkinson's) 3. iatrogenic (e.g. chemotherapy) |
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What are the three causes of apoptosis?
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1. physiologic (programmed)
2. pathologic (e.g. removal of damaged tissue or disease like Parkinson's) 3. iatrogenic (e.g. chemotherapy) |
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What are some morphological changes that occur during apoptosis?
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- villi are lost
- nuclear material condenses at edges of envelope -cell shrinks - DNA fractures -apoptotic bodies break off |
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Are membranes broken during necrosis? Apoptosis?
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necrosis: yes
apoptosis: no |
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Does necrosis cause swelling? Apoptosis?
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necrosis: yes
apoptosis: no |
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What kinds of cells have high turnover? Low turnover? Almost no turnover?
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High: marrow, epithelium, mucosa, fibroblasts
Low: hepatocytes, endothelium, bone No: osteocytes |
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Which immune cells are involved in apoptosis?
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cytotoxic lymphocytes and natural killer cells
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What are the two kinds of proteins we discussed re apoptosis?
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caspases and the Bcl-2 family
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What are caspases? What are the two kinds?
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They are endoproteases, meaning they cleave proteins from the inside. They are called "executor" proteins.
There are initiator and effector caspases, both of which are activated inside the cell. |
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What are the major features of caspases?
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- endoproteases
- exist as inactive zymogens - the initiators dimerize - the effectors break down the cytoskeleton and DNA |
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What is the Bcl-2 family of proteins?
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Proteins in mitochondria involved in apoptosis. There are pro-apoptotic and anti-apoptotic kinds. The relative balance determines which will prevail.
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When pro-apoptotic Bcl-2 opens holes in the mitochondria, what escapes?
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cytochrome C and AIF (apoptosis inducing factor), both of which activate initiator caspases
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What are the two pathways for initiating apoptosis (on the cellular level)?
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extrinsic: death receptors on cell surface
intrinsic: e.g. Bcl proteins |
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What is dynamic reciprocity?
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the process by which the ECM conveys info to the cell and vice versa
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What are some functions of the ECM?
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mechanical support, compartmentalizing, sequestering growth factors, allowing migration of embryonic cells
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Four components of ECM
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1. collagens
2. elastic fibers 3. proteoglycans 4. fibronectin (what about mineral?) |
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What type of collagen is found in bone and dentin?
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type 1
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What type of collagen is found in the PDL?
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types 1 and 3
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What type of collagen is found in cartilage?
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types 2 and 11
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What is the structure of collagen?
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Gly-X-Y, with X often proline and Y often hydroxyproline.
Gly is in the center of the triple non-alpha helix. The peptide bond is in the center, making is resistant to proteolysis. |
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What are the substrates for proline hydroxylation?
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proline, molecular oxygen, and alpha-ketoglutarate
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How does lack of vitamin C cause scurvy?
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During the hydroxylation of Pro during collagen synthesis, the cofactor Fe must be reduced. Vit C is required for this reduction. Without hydroxylation, the collagen is weak.
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During collagen synthesis, which processes occur in the RER?
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- synthesis of pre-procollagen
- hydroxylation of Pro and Lys - some glycosylation - self-assembly to procollagen |
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During collagen synthesis, what occurs in the Golgi?
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- some glycosylation
- Golgi secretes procollagen in vescicles |
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During collagen synthesis, what occurs outside the cell?
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the N and C propeptides are cleaved and the collagen monomers polymerize
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What are the nonhelical tails of collgen? Which amino acid residue is important here?
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Telopeptides. The Lys residues here will be oxidized to aldehydes and will begin cross-linking.
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What are the three types of collgen structure? What determines the distinction?
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They are based on the prevalence of non-helical domains.
1. Fibril-forming (1,2,3,5,11, all dental stuff) 2. Fibril-associated 3. Network-forming (type 4, still a procollagen) |
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What is endostatin?
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It's a propeptide of collagen type 18. It might stop tumors from vascularizing.
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Osteogenesis imperfecta and Ehlers-Danlos syndrome are both associated with defects in what?
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collagen
OI: Gly is replaced EDS: lysyl oxidase inactive |
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Marfan syndrome and Williams syndrome are both associated with defects in what?
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elastic fibers
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What kind of collagen appears in the PDL during eruption?
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Type 12
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Both elastic fibers and collagens cross-link via what?
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Lysines oxidated to aldehydes by lysyl oxidase
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What are the three components of elastic fibers?
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1. elastin
2. fibrilln 3. microfibrils |
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Which component of elastic fibers is deposited first?
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microfibrils (elastin fills in the scaffold)
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Elastic fibers are synthesized by ____ and _____.
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smooth muscle cells; fibroblasts
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What is the major proteoglycan of cartilage? What is its basic structure?
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Aggrecan. It's an aggrecan core with multiple GAGs (keratin sulfate, chondroitin sulfate) attached. Many aggrecans attach to a hyaluoronic acid core.
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Describe the basic structure of a proteoglycan.
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A protein core with covalently attached GAGs
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What are heparan sulfate rich proteoglycans?
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They regulate the availability of growth factors. They are found on cell surfaces. Syndecan and glypican are example
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What are the three components of elastic fibers?
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1. elastin
2. fibrilln 3. microfibrils |
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How does syndecan relate to FGF?
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FGF is bound to an intercellular PG. It then binds to the heparan sulfate of a syndecan, inducing a conformational change, allowing the FGF to bind to its cell-surface receptor.
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What is unique about hyaluoronic acid?
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It is a GAG that does not attach to a protein core. In fact, in the case of aggrecan, it is the core.
It expands when hydrated. |
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Which component of elastic fibers is deposited first?
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microfibrils (elastin fills in the scaffold)
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Elastic fibers are synthesized by ____ and _____.
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smooth muscle cells; fibroblasts
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What is the charge of GAGs?
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They're negative because of sulfate and carboxyl groups.
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Describe the basic structure of a proteoglycan.
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A protein core with covalently attached GAGs
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Where does one find hyaluoronic acid?
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This GAG is found in cartilage, synovial fluid and loose connective tissue.
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What is the major proteoglycan of cartilage? What is its basic structure?
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Aggrecan. It's an aggrecan core with multiple GAGs (keratin sulfate, chondroitin sulfate) attached. Many aggrecans attach to a hyaluoronic acid core.
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What are heparan sulfate rich proteoglycans?
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They regulate the availability of growth factors. They are found on cell surfaces. Syndecan and glypican are example
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How does syndecan relate to FGF?
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FGF is bound to an intercellular PG. It then binds to the heparan sulfate of a syndecan, inducing a conformational change, allowing the FGF to bind to its cell-surface receptor.
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What is unique about hyaluoronic acid?
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It is a GAG that does not attach to a protein core. In fact, in the case of aggrecan, it is the core.
It expands when hydrated. |
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What are the three components of elastic fibers?
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1. elastin
2. fibrilln 3. microfibrils |
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Which component of elastic fibers is deposited first?
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microfibrils (elastin fills in the scaffold)
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Elastic fibers are synthesized by ____ and _____.
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smooth muscle cells; fibroblasts
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Describe the basic structure of a proteoglycan.
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A protein core with covalently attached GAGs
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What is the major proteoglycan of cartilage? What is its basic structure?
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Aggrecan. It's an aggrecan core with multiple GAGs (keratin sulfate, chondroitin sulfate) attached. Many aggrecans attach to a hyaluoronic acid core.
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What are heparan sulfate rich proteoglycans?
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They regulate the availability of growth factors. They are found on cell surfaces. Syndecan and glypican are example
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How does syndecan relate to FGF?
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FGF is bound to an intercellular PG. It then binds to the heparan sulfate of a syndecan, inducing a conformational change, allowing the FGF to bind to its cell-surface receptor.
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What is unique about hyaluoronic acid?
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It is a GAG that does not attach to a protein core. In fact, in the case of aggrecan, it is the core.
It expands when hydrated. |
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What is the charge of GAGs?
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They're negative because of sulfate and carboxyl groups.
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Where does one find hyaluoronic acid?
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This GAG is found in cartilage, synovial fluid and loose connective tissue.
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The ECM works with ____ to induce angiogenesis.
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VEGF
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The ECM workds with ____ to resorb bone.
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osteoclasts
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The ECM induces ____ to migrate to wound sites.
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clot-forming cells
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What are the two major ECM receptors you will find on cell surfaces?
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integrins and syndecans
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What are the three adhesive proteins of the ECM that we discussed?
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fibronectin, osteopontin, and laminin
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FN is produced by ___ and ____.
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fibroblasts; hepatocytes
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FN is a ___ with up to 400 possible combinations. The cell binding domain consists of two ___ modules, which have tightly folded____ domains.
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dimer; Type III; beta-sandwich
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The FN-III (10) has an ____, which is bound by a specific integrin on the cell.
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RGD loop
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Osteopontin. Go.
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It's an adhesive protein of the ECM. It binds with an integrin on osteoclasts via its RGD loop.
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Laminin. Go.
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Found only in basement membranes. No RGD loop. Trimer.
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The basal lamina has ____ collagen.
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Type 4
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Describe the "inside-out" signaling of integrins.
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A ligand binds the receptor, which signals the cytoplasmic tail of the integrin. The integrin "straightens up" and binds the ECM.
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Integrins have ___ binding affinity for ECM binding adhesion proteins.
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low
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Focal adhesions connect the ___ of the cell to the ____ of the ECM via an integrin.
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actin filaments; fibronectin
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Hemidesmosomes connect the ____ of the cell to the ____ of the ECM (basal lamina) via an integrin.
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keratin filaments; laminin
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What disease occurs when the dermal-epidermal junction is weak?
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epidermolysis bullosa
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Fibronectin can bind to both integrins and ______, such as syndecan, at the same time.
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surface proteoglycans
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What are some examples of excessive ECM degradation?
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periodontal disease, rheumatoid arthritis
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Some cancer cells over express ____, which allow them to destroy the ECM and metastasize..
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collagenases
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What are matrix metalloproteins (MMPs)? What mutation did we discuss?
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They degrade components of the ECM. They are secreted during development, angiogenesis, in bones, etc. MMP-20 mutation will cause amelogenesis imperfecta.
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Osteoporosis is diagnosed when ____ is more than 2.5 SD below the average for a young, healthy adult.
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bone mineral density (BMD)
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Which products of bone formation will be present in blood/urine? Of bone breakdown?
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Formation: N and C collagen propeptides
Breakdown: telopeptides of collagen |
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What might cause juvenile osteoporosis? When does it manifest?
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diabetes, smoking, inactivity, poor diet....
Manifests in prepuberty |
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Compact bone is about __% mineralized. Trabecullar bone is about ___% mineralized.
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80; 20
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Where can osteoporosis often be seen in dental radiographs?
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the cortical bone of the mandible
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What is a potential complication of the use of bisphosphonate for treatment of osteoporosis?
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osteonecrosis of the jaw (ONJ)
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Bisphosphonates inhibit ___ function.
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osteoclast
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How do bisphosphonates work?
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They inhibit the formation of farnesyl PP. W/o FPP, GPP cannot create the ruffled border of osteoclasts. They cannot function.
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What is Prolia?
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It's an osteoporosis drug that binds to RANKL, inhibiting osteoclast formation.
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How can PTH injections treat osteoporosis?
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With sustained PTH levels, as is intuitive, OPG production goes down, RANKL goes up, and more osteoclasts are formed.
However, when PTH levels are spiked intermittently with injections, the effect is opposite and bone increases. |
