Biochemistry 2

Front 1

Stroma refers to...

Back 1

Cells embedded in the extracellular matrix

Front 2

Extracellular matrix is secreted by these cells

Back 2

Fibroblasts

Front 3

Stromal cells are derived from this cell lineage

Back 3

Mesodermal

Front 4

The layer separating epithelia from connective tissue is called the:

Back 4

Basal Lamina

Front 5

Three ways ECM regulates cell function?

Back 5

-signaling through surface receptors (integrins)

-Regulating growth factor signals

-Degradation products from ECM can affect cell function

Front 6

Fibronectin, laminin, and vitronectin all serve this purpose in the ECM

They are these type of ECM proteins

Back 6

Help cells attach

fibrous, adhesive

Front 7

Collagens are these type of molecules made of these type of chains:

Back 7

Trimeric; alpha

Front 8

A collagenous domain is:

Back 8

A triple helical region where every third AA is a glycine

Front 9

Collagens are divided into these types:

Back 9

Fibrillar, non-fibrillar

Front 10

"long unbranched polysaccharides consisting of a repeating disaccharideunit" describes:

Back 10

Glucosaminoglycans

Front 11

The main collagen in tendons, bone, ligaments, dentin, and skin is:

Back 11

Type 1

Front 12

Where is type 2 collagen?

Back 12

Mainly in the cartilage matrix

Front 13

OI results from a mutation of either one of these genes, which code for:

Back 13

COL1A1, COL1A2; type 1 collagen

Front 14

Chrondrodysplasias result from a mutation in this type of collagen gene

Back 14

Type 2

Front 15

Type one collagen is a ___trimer, and type two collagen is a ___trimer

Back 15

hetero, homo

Front 16

Type IV and type VI collagen can be found where?

Back 16

Basement membranes

Front 17

The anchoring fibrils that attach epithelia to the underlying tissue are composed of this type of collagen

Back 17

Type VII

Front 18

Dystrophic epidermis bullosa is a result of a mutation in this gene that makes this type of collagen

Back 18

COL7A1, Type VII

Front 19

A highly glycosolated protein is called a:

Back 19

Proteoglycan

Front 20

Dentinogingival/Alveogingival collagen serves this function:

Back 20

Holds free gingiva onto tooth

Front 21

What kind of collagen encircles the tooth?

Back 21

Circumferential

Front 22

What kind of collagen holds attached gingiva to bone?

Back 22

Periosteal

Front 23

This type of collagen runs between teeth

Back 23

Transseptal

Front 24

What type of fibers provide elasticity for tooth movement? Where are they located? What are they made of?

Back 24

Oxytalan fibers; periodontal ligament; fibrillin

Front 25

A mature collagen model to be used to make collagen fibrils is called:

Back 25

Tropocollagen

Front 26

Vitamin C is a cofactor for these hydroxylases which serve this function:

Back 26

prolyl, lysyl; hydroxylates prolines and lysines before triple helix formed.

Front 27

The collagen triple helix is right or left handed?

Back 27

Right

Front 28

A single collagen helix is right or left handed?

Back 28

Left

Front 29

Osteogenesis imperfecta types I, II, III, IV are all ___ ___ whereas types VII thru XVI are ___ ___

Back 29

autosomal dominant, autosomal recessive

Front 30

The most severe form of OI is:

Back 30

Type 2

Front 31

The most common form of OI leads to this happening with collagen:

Back 31

Trimers form, but less normal collagen 1 made

Front 32

In type 2 OI, this happens to collagen

Back 32

Abnormal pro-collagen chains are formed, breaking gly-x-y pattern, resulting in bad collagen (few normal collagen trimers)

Front 33

Progressive deforming/easily fractured bone OI is also called Type ___ OI

Back 33

3

Front 34

These types of OI don't have mutations in collagen I genes

Back 34

Types V, VI, VII

Front 35

Type 1 DI is associated with this disease

Back 35

OI

Front 36

DSPP mutations yield this disease

Back 36

Type II DI

Front 37

Goodpasture syndrome results from autoantibody attack on this type of collagen

Back 37

IV

Front 38

Type III and type V collagen mutations will often result in this disease

Back 38

Ehlers-Danlos syndrome

Front 39

Alport's syndrome, glomerular filtration issues, and basement membrane problems are often a result of a mutation in this type of collagen gene:

Back 39

IV

Front 40

Mutations in type VII collagen often result in this disease:

Back 40

Epidermolysis bullosa

Front 41

This molecule is expressed in high volumes in osteoblasts:

Back 41

Alkaline phosphotase

Front 42

Osteoblasts produce a lot of this type of collagen

Back 42

Type 1

Front 43

Hypophosphatasia is a result of a mutation in the gene that produces this, which serves this function:

Back 43

Alkaline phosphatase; hydrolyzes an inhibitor of mineralization to deactivate it, promoting increase in phosphate concentration to increase local mineralization

Front 44

TNSALP codes for:

Back 44

Alkaline phosphatase

Front 45

Mutations in RUNX2 result in this disease:

Back 45

Cleidocranial dysplasia

Front 46

Missing clavicles and supernumary teeth are symptoms of this disease:

Back 46

Cleidocranial dysplasia

Front 47

"ectopicmineralization in non-skeletal soft tissues, leading to sheets, plates of bonesforming across the ribs, joints" describes this disease:

Back 47

Fibrodysplasia Ossificans Progressiva (Stone man syndrome)

Front 48

Stone man syndrome occurs as a result in the mutation of this gene

Back 48

ACVR1

Front 49

Mutations in ACVR1 result in this disease, and the gene codes for this type of protein:

Back 49

Fibrodysplasia ossificans progressiva; BMP Type 1 receptor

Front 50

What is the morphological result of reduced amounts of sclerostin?

Back 50

Increased bone mass

Front 51

Sclerostosis and Van Buchem's diseases will occur as a result of the mutation of this protein:

Back 51

SOST- codes for sclerostin

Front 52

When bones are unnaturally dense yet prone to fracture, you are dealing with this disease

Back 52

Osteopetrosis

Front 53

Mutations in genes required to code proteins for osteoclast resorption often result in this disease

Back 53

Osteopetrosis

Front 54

In osteoporosis, what is the problem that generates the disease in regards to bone cellular functions?

Back 54

Bone resorbed by osteoclasts will not be sufficiently regenerated by osteoblasts

Front 55

An anti-resorptive agent does what?

Back 55

Inhibits bone resorption

Front 56

What's the name of a drug that stimulates bone formation?

Back 56

Bone anabolic agent

Front 57

WNT/Beta-catenin is involved in these four steps in regards to bone cell differentiation:

Back 57

-Mesenchymal stem cells to osteoprogenitors

-Osteoprogenitors to immature osteoblasts

-Maturation of osteoblasts

-Differentiation of osteoblasts (into osteocytes, apoptosis, or lining cells)

Front 58

Activating LRP5 mutations will do this to bone mass, whereas inactivating mutations will do this:

Back 58

-Activating: increase

-Deactivating: decrease

Front 59

BMP's 2 and 7 are essential for this step in bone cell development:

Back 59

Differentiation of mesenchymal cells to osteoprogenitor cells

Front 60

What is the official term for bone that forms in the wrong place?

Back 60

Heterotopic bone formation

Front 61

Bone that is dead without viable osteocytes is called:

Back 61

Osteonecrotic bone

Front 62

From what cells do osteoclasts originate?

Back 62

Hematopoietic cells; specifically macrophage/monocyte lineage

Front 63

Osteoclasts regulate these two other aspects of bone formation:

Back 63

-Activity of osteoblasts; phosphate homeostasis

Front 64

Osteoclastic resorption is required for these essential bone-building processes:

Back 64

-Longitudinal bone growth

-Tooth eruption

-Orthodontic tooth movement

Front 65

Use of bisphosphonates (which do what?) is associated with this disorder of bone:

Back 65

Inhibits bone resorption; osteonecrosis of the jaw

Front 66

What is the lifespan of osteocytes?

Back 66

Decades

Front 67

The inhibitor sclerostin is secreted via these cells to affect these cells

Back 67

osteocytes; osteoblasts

Front 68

FGF23, DMP1, PHEX, and MEPE are all expressed by this type of cell and serve this general function

Back 68

Osteocytes; regulate phosphate homeostasis

Front 69

How long is the lifespan of osteoclasts?

Back 69

Days

Front 70

What is the "master transcriptional factor" for osteoclasts?

Back 70

NFATc1

Front 71

Osteopetrosis can result from impaired function of this type of cell

Back 71

Osteoclasts

Front 72

What is the normal range for serum calcium concentration? (mg/dL)

Back 72

8.5-10.5 mg/dL

Front 73

What is the biologically active fraction of calcium in the serum? (%)

What form is this calcium in?

Back 73

45%; ion

Front 74

How much calcium is absorbed daily by the gut? How much is excreted daily in the urine?

How much calcium is released daily in bone? How much calcium is deposited daily in bone?

Back 74

Gut: 200mg

Bone: 500mg

Front 75

How much dietary phosphorus is absorbed via the gut? (% range)

Back 75

80-90%

Front 76

What is the standard serum Pi range? (mg/dL)

Back 76

2.5-4.5mg/dL

Front 77

TRP's serve what function in calcium homeostasis?

Back 77

Uptake from apical side of cell

Front 78

What do calbindins do?

Back 78

transcellular support of calcium

Front 79

What is responsible for extrusion of calcium on the basal surface of the cell?

Back 79

Calcium ATPases or Na dependent calcium exchangers

Front 80

What are the three steps of calcium uptake?

Back 80

-Uptake from apical side

-Transcellular transport

-Extrusion from basal surface

Front 81

What transporter takes up phosphate in the gut? What section of the gut is this transporter located?

Back 81

NaPi-IIb; ileum

Front 82

TRPV6 is responsible for what, where?

Back 82

Calcium uptake in the gut

Front 83

What are the major hormones regulated calcium homeostasis? (3)

Phosphate homeostasis? (3)

Back 83

Ca: PTH, Calcitriol (Vit.D), Calcitonin

PO4: PTH, Calcitriol, FGF23

Front 84

What organ releases calcitonin? What's the effect of this hormone on its three target organs?

Back 84

-Thyroid; decrease release of Ca in bone, decrease uptake of Ca in gut, decrease reabsorption of Ca in kidney

Front 85

Increasing calcium release from bone, increasing calcium uptake in the gut, and increasing reabsorption of calcium in the kidney are all effects of this hormone in response to this level of calcium in serum:

Back 85

PTH; low

Front 86

Where are calcium sensing receptors located?

Back 86

The parathyroid gland

Front 87

In the case of high serum calcium;

-Is CaSR signalling increased or decreased?

-Is PTH secretion increased or decreased?

Back 87

-CaSR signalling is increased.

-PTH secretion is decreased

Front 88

What effect does PTH have on phosphate reabsorption in the kidney?

Back 88

Decrease

Front 89

What's the function of PTH in regards to vitamin D? Where does this function occur?

Back 89

PTH stimulates the change of [25(OH)D3] to the active form of [1-25(OH)D3];the kidney

Front 90

What type of protein has its expression frequency changed by Vitamin D3? In what way?

Back 90

Calbindins; expression goes up

Front 91

What is the function of Vitamin D3 on PTH production?

Back 91

Inhibitory; decreases

Front 92

Vitamin D3 has three effects on phosphate homestasis. What are they?

Back 92

-Increased intestinal uptake

-Increased reabsorption in kidney tubules

-Increased release in to circulation from bone

Front 93

What belongs in the blue box? What belongs in the green box?

Back 93

Blue: PTH

Green: Vitamin D

Front 94

What cells respond directly to calcitonin? How?

Back 94

Osteoclasts; retract their ruffled border

Front 95

When is FGF23 expression induced? Where?

Back 95

When serum phosphate is too high- primarily in osteocytes, but also in o-blasts, lining cells, etc

Front 96

What is the main mechanism for phosphate homeostasis regulation?

Back 96

Kidney reabsorption

Front 97

PTH has what effect on phosphate reabsorption? How?

Back 97

Inhibits; by inhibiting NaPiIIa and NaPiIIc in the kidney tubules

Front 98

FGF23 has what effect on serum phosphate?

Back 98

Lowers

Front 99

Net effects of PTH, calcitonin, FGF23, and Vitamin D on Ca and PO4 serum levels?

Back 99

PTH: Calcium up, phosphate down

Calcitonin: Calcium down

Vitamin D: Calcium up, phosphate up

FGF23: Phosphate down

Front 100

Six symptoms of hypocalcemia?

Back 100

-Muscle cramping

-Increased neuromusc. excitability

-Muscle spasms

-Fatigue

-Cardiac dysfunction

-Depression, psychosis, seizures

Front 101

Hypoparathyroidism can result in this status in regards to serum calcium levels

Back 101

Hypocalcemic

Front 102

Pseudohypoparathyroidism results from this bodily response to PTH; results in this status in regards to serum levels of calcium:

Back 102

PTH resistance; hypocalcemic

Front 103

Mutations in VDR or 1-alpha hydroxylase result in this disease:

This condition has this effect on serum calcium levels

Back 103

Rickets; vitamin D resistance.

Decreases serum calcium levels (hypocalcemic)

Front 104

DiGeorge syndrome is associated with this irregular anatomy, and results in this classified disorder

Back 104

Lack of parathyroid glands; hypoparathyroidism

Front 105

Activating CaSR mutations results in what physiological response, and what blood serum outcome?

Back 105

Decreased calcium reabsorption in kidney as a result of incorrect reading of calcium levels as high by CaSR and parathyroid; leads to hypocalcemia

Front 106

Osteomalacia manifests in this symptom

Back 106

Soft bones- as a result of a failure of osteoid to calcify

Front 107

Type 1 Vitamin D dependent rickets results from a mutation in this:

Back 107

renal 25-OH-vitamin D-1α-hydroxylase

Front 108

The serum difference which distinguishes VDDR1 and 2 is:

Back 108

VDDR1 has very low serum Vitamin D3. VDDR2 has very high serum VD3.

Front 109

Vitamin D Dependent Rickets Type 2 is caused by:

Back 109

Defects in the Vitamin D receptor

Front 110

Which type of VDDR is associated with alopecia?

Back 110

VDDR2

Front 111

Oversecretion of PTH not responsive to CaSR signalling results in:

Back 111

Hyperparathyroidism

Front 112

Mutations in tumor suppressor genes can lead to tumors in endocrine tissues. What is the name of these tumors, and what are 2 genes which can be mutated to result in them?

What is the serum molecular alteration that results?

Back 112

Multiple endocrine neoplasias; MEN1, MEN2A

Front 113

Chronic renal failure can result in this type of hyperparathyroidism.

What's the other condition that can bring about this type of hyperparathyroidism?

Back 113

Secondary

-Vitamin D malabsorption

Front 114

XLH is due to mutations in what gene? What does this gene do?

Back 114

PHEX; inhibits FGF23 production. (leads to hypophosphatemia because FGF23 never inhibited, endlessly produced

Front 115

What disease results from mutations in FGF23 disabling its cleavage? How does this affect phosphate levels?

Back 115

Autosomal dominant hypophosphatemic rickets (ADHR); decreases phosphate levels because FGF23 is never destroyed

Front 116

What does DMP1 do? What disease results from the mutation of DMP1?

Back 116

DMP1 inhibits FGF23 production. Autosomal recessive hypophosphatemic rickets results from mutation of DMP1.

Front 117

Loss of function mutation is NaPiIIc results in what disease? What is the result of this mutation?

Back 117

Hereditary hypophosphatemic rickets with hypercalciuria (HRHH)

-Inefficient reabsorption of Pi in kidney.

Front 118

Tumor induced osteomalacia happens because:

Back 118

Tumors secrete FGF23 into the bloodstream. Lowers Pi independent of serum concentration levels

Front 119

Inactivating mutations in FGF23 can lead to this serum status:

Back 119

Hyperphosphatemia

Front 120

What are familial tumoral calcinoses?

Back 120

Inherited disorders which result in an excess of serum phosphate- hyperphosphatemic state

Front 121

What are the four phases of skeletal formation?

Back 121

-Migration of preskeletal cells

-Interaction of these cells with epithelial cells

-Mesenchymal condensation

-Differentiation to chondroblasts or osteoblasts by mesenchymal cells

Front 122

During fracture repair, this method of bone formation is used. It is the primary method of bone formation for most bones in the body

Back 122

Endochondral

Front 123

This method of bone formation could be referred to as indirect. Why?

Back 123

Endochondral; mesenchyme forms a cartilaginous template first

Front 124

When mesenchymal cells differentiate directly into osteoblasts, this type of ossification has occurred:

Back 124

Intramembranous

Front 125

In bony remodeling, what type of bone do we start with, and what type do we end up with?

Back 125

Woven changes to lamellar

Front 126

Compact and cancellous bone are both subgroups of this type of bone:

Back 126

Lamellar/(secondary)

Front 127

Trabecular bone is another name for this type of bone:

Back 127

Cancellous

Front 128

Haversian canals occur in this type of lamellar bone

Back 128

Compact

Front 129

What are the four stages of fracture repair?

Back 129

1) Formation of hematoma

2) Formation of fibrocartilage callous

3) Tissue metaplasia; we switch that fibrocartilage out for bone

4) Remodeling and turnover occurs to attempt to make bone look like what it was before break

Front 130

Inflammatory cytokines associated with hematoma? (5)

Back 130

-TNF-alpha

-Interleukins (IL) 1, 6, 11, 18

Front 131

What lays down the fibrous connective tissue matrix of the first callous in fracture repair?

Back 131

Fibroblasts

Front 132

In hypoxic regions post-fracture, what step initiates endochondral ossification?

Back 132

Mesenchymal stem cells differentiate into chondrocytes

Front 133

Osteogenic precursor cells come primarily from this tissue layer

Back 133

Periosteum

Front 134

The first bone that appears in the formation of a bony callous is of this type:

Back 134

Woven

Front 135

What are three angiogenic factors involved in the fracture repair process?

Back 135

-PDGF

-VEGF

-ANGPT (angiopoietin)

Front 136

What are the three TGF-beta superfamily members involved in bone repair?

Back 136

-TGF-beta

-BMP-2

-GDF-8

Front 137

What are the two primary roles of TGF-beta superfamily growth factors?

Back 137

-Promote ECM synthesis, and assembly/initiation of callous formation

-Promote osteogenic differentiation

Front 138

Macrophages, mesenchymal cells, and inflammatory cells secrete these small chemical signals during bone repair

Back 138

Inflammatory cytokines

Front 139

High strain on an area undergoing fracture healing has what effect?

Back 139

Promotes fibrous tissue

Front 140

What conditions promote cartilage formation in bone repair?

Back 140

Intermediate strain, low O2 tension.

Front 141

Low strain and high O2 tension promotes what substance to form during fracture healing?

Back 141

Intramembranous Bone

Front 142

In fracture healing, what releases TGF-beta?

Back 142

Platelets in hematoma

Front 143

Cartilage is vital for this type of bone formation

Back 143

Endochondral

Front 144

What collagen types predominate hyaline cartilage?

Back 144

II, X

Front 145

Elastic cartilage is found in these three locations:

Back 145

-Eustachian tubes

-Epiglottis

-Ear lobes

Front 146

The pubic symphysis, TMJ, and intervertebral disks are all composed of this type of cartilage:

Back 146

Fibrocartilage

Front 147

Type 1 and Type 2 collagen make up the extracellular matrix of this type of cartilage:

Back 147

Fibrocartilage

Front 148

What is the master transcriptional factor for endochondral bone formation?

Back 148

SOX9

Front 149

Hypertrophic chondrocytes produce this growth factor which stimulates angiogenesis

Back 149

VEGF

Front 150

When is SOX9 turned off? What is turned on to signal the next stage of bone genesis?

Back 150

The hypertrophic stage of epipheseal plate growth; RUNX2, Osterix

Front 151

IHH, PTHrP, VEGF, and FGFs all represent this class of molecules and are involved in this phase of bone formation

Back 151

Signalling molecules; chondrocyte differentiation

Front 152

Where is PTHrP expressed? What does it do?

Back 152

The ends of bones during bone growth; keeps pre-hypertrophic cells proliferating and prevents them from entering hypertrophic phase

Front 153

What stage of cell growth in bone formation promotes production of Indian Hedgehog Protein (IHH)?

What's the function of IHH?

Back 153

Hypertrophy; Stimulates PTHrP production to keep chondrocytes proliferating in the pre-hypertrophic phase

Front 154

What type of signaling inhibits chondrocyte proliferation? What type promotes it?

Back 154

FGF; BMP

Front 155

Achondrodysplasia comes as a result of mutation in which gene?

Back 155

FGFR3

Front 156

Dwarfism as a result of a mutation in FGFR3 gene is a symptom of this greater systemic disease

Back 156

Achondrodysplasia

Front 157

What is the main proteoglycan in cartilage?

Back 157

Aggrecan

Front 158

Loss of function mutation in SOX9 results in what disease? What is the genetic pattern of expression for this kind of mutation?

Back 158

Camplomelic Dysplasia; Autosomal dominant

Front 159

What is the receptor of IHH? PTHrP?

Back 159

PTC1; PTH1R

Front 160

FGFR3;

-Expressed where?

-Functions (2)?

Back 160

-Proliferating chondrocytes

-Limits chondrocyte proliferation,

-Suppresses IHH

Front 161

Stickler syndrome demonstrates this level of disease severity; results from a mutation in this gene:

Back 161

Mild; Type 2 collagen

Front 162

Spondyloepiphyseal dysplasia results from a mutation in this gene, and demonstrates with this phenotype

Back 162

COL2A1; dwarfism

Front 163

What does aggrecan assemble with in order to form giant aggregates?

Back 163

Hyaluronan

Front 164

How many articular surfaces are present in the TMJ?

Back 164

3

Front 165

Intrascapular TMJ disorders are referred to as being of the ___ type

Back 165

articular

Front 166

Rheumatoid arthritis can lead to this type of TMJ disorder

Back 166

Articular