A unified model for the action of leptin on bone turnover.
Leptin has been advocated as a centrally acting factor responsible for inhibiting accumulation of bone mass. However, recent investigations unequivocally establish leptin as a local (autocrine) factor expressed by osteoblasts. Exogenously added leptin causes osteoblastic cell proliferation and differentiation, while also rendering osteoblasts more efficacious in terms of mineralization. Leptin acts as an anti-apoptotic agent, and augments messages responsible for the remodelling of bone tissue, i.e., mRNAs for osteoprotegerin (OPG) and the interleukin IL-6. Furthermore, leptin message is readily expressed in osteoblasts subjected to mechanical strain. In this respect, osteoblasts, which are unilaterally stretched proliferate and differentiate, a phenomenon being potentiated by exposure of the cells to differentiating humoral factors. This article discusses a unified model of dually acting leptin through the central nervous system and the mechanostat principle applied to osteoblasts. The proposed model may account for the finely tuned bone homeostasis maintained within rather narrow limits, depending on exposure to humoral factors and the prevailing mechanostat usage mode.
Gordeladze
Jan O
JO
Institute of Medical Biochemistry, University of Oslo, Blindern, Norway. j.o.gordeladze@basalmed.uio.no
Reseland
Janne E
JE
D000818:Animals; D001857:Bone Matrix / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology*; D001842:Bone and Bones / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D009119:Muscle Contraction; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D053244:Osteoprotegerin; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D054411:Receptors, Leptin; D018124:Receptors, Tumor Necrosis Factor
D006023:Glycoproteins; D015850:Interleukin-6; C515448:LEPR protein, human; D020738:Leptin; D053244:Osteoprotegerin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D054411:Receptors, Leptin; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; C506031:Tnfrsf11b protein, mouse; C515447:leptin receptor, mouse