An age-dependent interaction with leptin unmasks ghrelin's bone-protective effects.
The mutual interplay between energy homeostasis and bone metabolism is an important emerging concept. Ghrelin and leptin antagonize each other in regulating energy balance, but the role of this interaction in bone metabolism is unknown. Using ghrelin receptor and leptin-deficient mice, we show that ghrelin has dual effects on osteoclastogenesis, inhibiting osteoclast progenitors directly and stimulating osteoclastogenesis via a more potent systemic/central pathway. Using mice with combined ghrelin receptor and leptin deficiency, we find that this systemic osteoclastogenic activity is suppressed by leptin, thus balancing the two counterregulatory ghrelin pathways and leading to an unchanged bone structure. With aging, this osteoclastogenic ghrelin pathway is lost, unmasking the direct protective effect of ghrelin on bone structure. In conclusion, we identify a novel regulatory network linking orexigenic and anorectic metabolic factors with bone metabolism that is age dependent.
Department of Internal Medicine, Erasmus University Medical Center's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
Martijn
M
van der Velde
Bram C J
BC
van der Eerden
Yuxiang
Y
Sun
Julia M M
JM
Almering
Aart-Jan
AJ
van der Lely
Patric J D
PJ
Delhanty
Roy G
RG
Smith
Johannes P T M
JP
van Leeuwen
D000367:Age Factors; D000818:Animals; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism*; D054439:Ghrelin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D020738:Leptin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction
D054439:Ghrelin; D020738:Leptin