Connective Tissue/Bone Flashcards
(23 cards)
Structure of Collagen?
Glycine every 3rd AA
Hydroxyprolines or proline => cross-helix H bonding
Hydroxylysines=> corss lins between collagen
Triple helix
End/tail: clipped by procollagen peptidase
Assembled into fibrils in ECF
Precursor of all proteins?
mRNA
Steps of collagen synthesis?
mRNA => hydroxylation in ER/ Vit C dependent => attachment of soluble galactosyl/sugars to hydroxylsyl residues
Types of collagen and their role in disease?
Type I: skin/tendons/ligaments => OI types I-IV, osteoporosis
Type II: hyaline cartilage/vitreous humor/eye => Types II/XI collagenopathies
Type III: skin/muscle/intestine/glands => Ehlers-Danlos syndrome, aneurysms
Type IV: forms sheets, not fibers => HANAC, familial benign heaturia, Goddpasture’s syndrome
3 dominant types of fibers in CT?
Collagenous
Elastic
Reticular fibers
Characteristics of different fiber types?
Collageneous: composed of collagen/fibrils 1/4 of protein in body
Reticular: type III in liver/muscle/bone marrow/lymph => supportive
Elastic: microfibrils => irregular/random coils => desmosine cross links => strength/elasticity
Inorganic vs organic bone matrix components?
Inorganic: from calcium hydroxyapatite
Organic: type I collagen = osteoid and growth factors = ground substance
Know pic Pg 22 and
31
Osteoblasts vs -clasts vs -cytes?
Osteoblast: produce bone/inorganic/organic/ground substance
Osteoclasts: modified monocyte/macrophage => resorption/cleavage of bone
Osteocytes: former osteoblasts trapped in organic bone, link via canaliculi/gap junctions
Steps of transforming growth factor-beta signaling?
Changes gene activity
Two TGF-beta proteins form dimer (cysteine knot)
=> interacts with T-beta-R-II => recruit T-beta-R-I => T-beta-R-II conformational change => phosphorylation of R-I => activate SARA => SMAD4/RSMAD
Osteoblast secrete? Produce
Type I collagen/Gp/proteoglycans
Ground substance composed of GAG, Gps
Cytokine M-CSF =>promote osteoclast growth/diff
Glycoproteins secreted by osteoblasts?
Osteocalcin
Osteonectin => mineralization process
Osteopontin => increased by calcitriol/Vit D3
Positive and negative regulation of osteoclasts?
Positive: RANKL/M-CSF
Receptor activator of nuclear factor kappa B Ligand
Negative: OPG by inhibiting RANK/NF-kB
Osteoprotegerin
Role of podosome?
Osteoclast adhesion mediating osteoclast-ECF interaction
Actin rich, attach to integrin receptor
Which chemical of osteoclasts degrades collagen matrix via selective cleavage of collagen?
Cathepsins like cathepsin K
Enzymes involved in break down of in/organic matrix by osteoclasts?
Asparate protease
Matrix metalloprotease
Most abundant bone cell?
Osteocyte
Bone growth regulation? Balance depends on? Hormones?
Remodeling/break down dependent on: FGF PDGF TGF-beta BMPs Polypeptide growth hormone (from pituitary)
Androgen/estrogen => promote osteoblast activity => promotes OPG => inhibits RANK
PTH
Bone resorption control?
Increased:
PTH
Vit D -> IL-6
M-CSF (also inhibits OPG)
Difference intramembraneous ossification vs endochondral ossification?
Intramembranous: skull, and during repair of fractures => direct bone deposition into CT
Endochondral: formation of all other long bones/flat/irregular/ continued growth during childhood/ fracture repair => starts with hyaline cartilage
3 phases of bone healing?
Reactive: minutes->days
Clot forms
Reparative phase: days-weeks
Remodeling: weeks-months
Selective resorption/redeposition until final compact bone matrix is produced
Relationship of PTH and calcitonin?
Antagonists
PTH increases Ca in serum:
PTH => increases reabsorption of Ca, Vit D in intestine/kidney
Bone: increase RANK => demineralization
Calcitonin: reduces blood Ca
Calcitonin => decreases Ca reabsorption, inhibits mineralization
Also secreted in response to gastrin
=> Gq receptor
Regulation of Ca/D ?
Ca in GI => absorption stimulated via 1,25 (OH)2D into blood and also stimulates mineralization
E2 stimulates mineralization
PTH stimulates reabsorption of Ca and mineralization
Calcitonin inhibits reabsorption of Ca and mineralization
