[CAS NO. 138977-28-3]  Capsazepine

Capsazepine(CPZ) at a concentration of 94.2 µg/ml (IC50 concentration of capsazepine) exhibits a statistically significant inhibition of osteoclast growth and proliferation. Capsazepine converts the NKA into Na-ATPase. CPZ inhibits K+-dependent activity but allows Na-ATPase associated with Na+ transport. CPZ has no effect on Na-ATPase measured in the absence of K+. CPZ also inhibits para-nitrophenyl phosphatase activity, albeit with a lower affinity. CPZ strongly reduces the steady-state EP level and the Na+ affinity for phosphorylation decreased 3-fold after CPZ treatment. In summary, CPZ blocks an Na+/K+ cycle in the NKA but leaves an Na+ cycle intact, reducing the transport stoichiometry of the pump. Capsazepine inhibits osteoclast formation and bone resorption in a dose dependent manner in bone marrow-osteoblast co-cultures and RANKL generated osteoclast cultures. Capsazepine also suppresses RANKL induced IκB and ERK1/2 phosphorylation and causes apoptosis of mature osteoclasts and also inhibits alkaline phosphatase activity and bone nodule formation in calvarial osteoblast cultures.