L-type calcium channels mediate mechanically induced bone formation in vivo.
Cell and tissue culture studies suggest that the long-lasting (L-type) voltage-sensitive calcium channels (VSCC) play a role in the signaling cascade in bone cells after mechanical loading. We investigated whether the L-type VSCC mediates mechanically induced bone formation in vivo using two L-type VSCC antagonists verapamil and nifedipine. Female Sprague-Dawley rats were divided into five groups: control group (Veh), two verapamil-treated groups (20 mg/kg, Vera-L; 100 mg/kg, Vera-H), and two nifedipine-treated groups (20 mg/kg, Nife-L; 100 mg/kg, Nife-H). One bout of mechanical loading was applied to the right tibia 90 minutes after oral administration of verapamil or 30 minutes after oral administration of nifedipine. Mechanical loading increased mineralizing surface (MS/bone surface [BS]), mineral apposition rate (MAR), and bone formation rate (BFR/BS) on the endocortical surface in loaded tibias of control animals compared with nonloaded (left) tibias. Verapamil and nifedipine suppressed the load-induced increase in BFR/BS observed in vehicle-treated controls by 56-61% (p < 0.01) and 56-74% (p < 0.01), respectively. Yet, significant differences in MS/BS and BFR/BS between right and left limbs were found in verapamil- and nifedipine-treated animals, indicating that the treatments did not completely abolish load-induced bone formation. This study shows that blocking the L-type calcium channel in vivo substantially suppresses the mechanically induced increase in bone formation that normally would occur and suggests that the L-type calcium channel mediates mechanically induced bone adaptation in vivo.
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D003864:Depression, Chemical; D005260:Female; D009543:Nifedipine / Q000494:pharmacology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D013977:Tibia / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D014700:Verapamil; D009543:Nifedipine
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