Opg - rank/rank-l

[Phloston]

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What is the actual mechanism by which OPG inhibits RANK/RANK-L?

How does IL-1 (osteoclast activating factor?) play a role in bone degradation? What's the mechanism?

 

[alternatego]

Osteoprotegerin is a decoy receptor for RANK-L (think etarnecept with TNF alpha).

Osteoclasts are derived from monocytes, and IL-1 contributes to their differentiation.

EDIT: The MSK section in Robbins Review of Path is awesome, you should check it out.

 

[Myxedema]

Osteoblasts activate osteoclast precursors by three mechanisms:

(1) They express RANK-L on their cell surface (as well as secreting soluble RANK-L), which binds to RANK receptors on osteoclast precursors and activate them.
(2) They decrease the secretion of osteoprotegerin OPG, which is a soluble decoy receptor for RANK-L. (Think etanercept)
(3) They secrete M-CSF, which binds to its receptor on osteoclast precursors.

As a result, osteoclast precursors differentiate into osteoclast.

 

[Phloston]

Osteoblasts activate osteoclast precursors by three mechanisms:

(1) They express RANK-L on their cell surface (as well as secreting soluble RANK-L), which binds to RANK receptors on osteoclast precursors and activate them.
(2) They decrease the secretion of osteoprotegerin OPG, which is a soluble decoy receptor for RANK-L. (Think etanercept)
(3) They secrete M-CSF, which binds to its receptor on osteoclast precursors.

As a result, osteoclast precursors differentiate into osteoclast.

Thanks for that.

My contribution back to you:

I've seen in a practice question that GM-CSF / G-CSF acts at a transmembrane receptor. It also stimulates JAK/STAT tyrosine kinases.

 

[Myxedema]

That's good, let me reply back:

- Growth factor receptors (e.g. EGFR): RTK
- GH, PRL and cytokine receptors: JAK/STAT

Bonus question: What is the name of the monoclonal antibody binding EGFR-1? (Hint: It's not trastuzumab)

 

[Phloston]

That's good, let me reply back:

- Growth factor receptors (e.g. EGFR): RTK
- GH, PRL and cytokine receptors: JAK/STAT

Bonus question: What is the name of the monoclonal antibody binding EGFR-1? (Hint: It's not trastuzumab)

Erythropoietin also acts via JAK/STAT btw.

Cetuximab targets EGFR. It's used for colon cancer (in combination with irinotecan). I had encountered this in a practice question somewhere.

I have a fetish for all of the monoclonal antibodies and have a list about twice as long as the one in FA. I had thought I may have just been wasting my time, but I had actually encountered Palivizumab in Kaplan QBank, so my time spent studying them paid off.