Modulation of osteoclast differentiation

Abstract

Provided are methods for treating a pathological condition associated with unbalanced osteoclast differentiation by providing an AQP-9 modulator. The modulator can be an AQP-9 inhibitor or an AQP-9 inducer. Also provided are methods for modulating osteoclast differentiation, methods for treating pathological conditions associated with unbalanced osteoclast differentiation, as well as pharmaceutical composition including such modulators.

1 .- 46 . (canceled) 
     
     
         47 . A method for modulating unbalanced osteoclast differentiation, comprising: providing osteoclasts, osteoclast precursor cells, or a mixture thereof, with an amount of an AQP-9 modulator, the amount of said modulator being effective to affect AQP-9 activity in one or more of said osteoclast cells and osteoclast precursor cells. 
     
     
         48 . The method according to  claim 47 , for inhibiting osteoclast differentiation, comprising: providing said osteoclasts, osteoclast precursor cells, or mixture thereof, with an amount of an AQP-9 inhibitor, the amount of said inhibitor being effective to reduce AQP-9 activity in one or more of said osteoclast cells and osteoclast precursor cells. 
     
     
         49 . The method according to  claim 48 , wherein said osteoclast precursor cells are mononuclear osteoclast cells. 
     
     
         50 . The method according to  claim 48 , wherein said AQP-9 activity is affected by reducing or preventing expression of said AQP-9 in said osteoclast, osteoclast precursor cells, or mixture thereof, or by blocking said AQP-9 activity in one or more of said osteoclast cells and osteoclast precursor cells. 
     
     
         51 . The method according to  claim 48 , wherein said AQP-9 inhibitor is an AQP-9 channel blocker, an AQP 9 expression inhibitor, or an AQP 9 translation inhibitor. 
     
     
         52 . The method according to  claim 48 , wherein an effect on the AQP-9 activity is exhibited by one or more of the following
 reduction in size of osteoclasts;   reduction in number of osteoclasts; and   reduction in number of nuclei in an osteoclast.   
     
     
         53 . The method according to  claim 47 , wherein said modulator is an AQP-9 inducer. 
     
     
         54 . A method for inducing osteoclast differentiation, comprising: providing osteoclasts, osteoclast precursor cells, or a mixture thereof, with an amount of an AQP-9 inducer, the amount of said inducer being effective to elevate AQP-9 activity in one or more of said osteoclast cells and osteoclast precursor cells. 
     
     
         55 . A method for treating a pathological condition associated with unbalanced osteoclast differentiation in a subject, comprising: administering to a subject in need thereof, a pharmaceutical composition comprising a therapeutically effective amount of an AQP-9 modulator, the amount of said AQP-9 modultor being effective to affect AQP-9 activity in unbalanced osteoclasts. 
     
     
         56 . The method according to  claim 55 , wherein said AQP-9 modulator is an AQP-9 inhibitor. 
     
     
         57 . The method according to  claim 55 , wherein said unbalanced osteoclast differentiation comprises excessive osteoclast differentiation. 
     
     
         58 . The method according to  claim 55 , wherein said pathological condition is associated with bone resorption. 
     
     
         59 . The method according to  claim 55 , wherein said pathological condition is osteoporosis, an inflammation-associated bone disease, a cancer-associated bone disease, an infection-associated bone disease, periodontal disease, or aseptic loosening of prosthetic implants. 
     
     
         60 . The method according to  claim 55 , wherein said pathological condition is osteoporosis, osteomyelitis, rheumatoid arthritis, or Paget's disease. 
     
     
         61 . The method according to  claim 56 , wherein said inhibitor is an AQP-9 channel blocker or an AQP-9 expression inhibitor. 
     
     
         62 . The method according to  claim 61 , wherein said AQP-9 channel blocker is phloretin. 
     
     
         63 . The method according to  claim 55 , wherein said AQP-9 modulator is an AQP-9 inducer. 
     
     
         64 . The method according to  claim 63 , wherein the pathological condition is associated with osteoclast deficiency. 
     
     
         65 . The method according to  claim 64 , wherein the pathological condition is associated with overly dense bones. 
     
     
         66 . The method according to  claim 65 , wherein said pathological condition is osteopetrosis. 
     
     
         67 . The method according to  claim 55 , wherein said AQP-9 modulator is administered to said subject by injection to said subject's bone marrow or to the subject's blood stream. 
     
     
         68 . The method according to  claim 55 , wherein said AQP-9 modulator is orally administered to said subject. 
     
     
         69 . A pharmaceutical composition comprising as an active ingredient an amount of AQP-9 modulator, the amount of said AQP-9 modulator being effective to affect AQP-9 activity in osteoclast cells or osteoclast precursor cells. 
     
     
         70 . The method according to  claim 48 , wherein said AQP-9 inhibitor is an AQP-9 expression inhibitor, or an AQP-9 translation inhibitor