Review Note
Last Update: 05/16/2024 11:33 PM
Current Deck: DS1 Winter::AN 715 Block 2
Published
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Text
- Signaling
- Osteoblasts
- {{c1::Mesenchymal}} origin
- transcription factors:
- {{c2::Runx-2}}: triggers expression of major bone proteins & maturation of osteoblasts.
- {{c2::Osterix}}: directs precursors toward osteoblast lineage.
- Absence of runx or osterix: {{c2::no intramembranous or endochondral bone formation}}.
- Wnt signaling promotes {{c3::bone formation}}.
- {{c3::SOST (Sclerostin)}} inhibits Wnt
- Wnt mutations -> {{c3::osteoporosis}}; SOST mutations -> {{c3::osteosclerosis}}
- {{c4::RANKL}} expressed on surface of osteoblasts;
- ({{c4::OPG}}) – a decoy for {{c4::RANKL}}
- Proinflammatory cytokines favor bone {{c4::loss}}
- In sum
- Have {{c5::RANKL}} on cell surface
- And have {{c5::OPG}} (decoy soluble receptor that binds to RANKL)
- w/o OPG means {{c5::higher osteoclast activity and bone resoprtion}}
- Osteoclast
- {{c6::Hematopoietic stem cell}} orgin
- Fusion of {{c6::mononuclear cells}} belonging to macrophage lineage and originating of monocytes
- {{c6::Interference in different linaages}} can lead to pathogenic conditions
- Mechanism
- attach to {{c7::mineralized surface}}
- create sealed {{c7::acidic}} environment via proton pump
- degrade organic matrix via {{c7::acid phosphatase}} and {{c7::cathepsin B}}
- take up {{c7::mineral and amino acids }}
- {{c7::transcytose}} from opposite side.
- Expression
- Express {{c8::RANK}}
- Characterized by {{c8::TRAP}}
- Influence osteoblasts
- In sum
- With {{c9::OPG, RANK}} is not open for bisiness
- w/o OPG, {{c9::osteoclast expresses RANK}}
- {{c9::Osteoglastogenensis}} occur
- Osteoblasts can influence differentiation of osteoclasts
- {{c10::RANK}} (osteoclast progenitors express) and {{c10::RANKL}} (osteoblasts & stromal cells express) interaction is involved
- osteoblasts express a {{c10::RANKL}} ”decoy” glycoprotein of TNF receptor family that {{c10::blocks osteoclast differentiation}} (osteoprotegerin).
- {{c11::Bone marrow}} stromal cells and chronically {{c11::activated/memory T-cells}} also influence osteoclasts.
- {{c11::Osteocytes}} may also
regulate RANKL:
- mechanical stress {{c11::decreases}} RANKL expression. Osteocytes respond to stress which is thought to increase fluid flow in canalicular network and stimulate osteocytes which in turn send messages to osteoblasts, etc.
- In sum
- What affects RANKL
- {{c12::Osteocytes, T cells}}
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