The control of bone growth by parathyroid hormone, leptin, & statins.
There is a need for anabolic drugs that can stimulate bone growth, improve bone microarchitecture, accelerate fracture healing and thus restore bone strength to oteoporotics. The anabolic agents currently leading the way to the clinic are the parathroid hormone (PTH) and some of its adenylyl cyclase-stimulating fragments. Here we discuss what is known about the genes and their products that are stimulated by PTHR1 receptor signals and in four ways cause a large accumulation of bone-building osteoblasts. We will also discuss the currently controversial anabolic activity of the cholesterol-lowering statins and outline a possible mechanism by which they might stimulate BMP-2 expession and bone growth. Finally, we will present the growing evidence for the body's "fat-o-stat" cytokine-leptin-indirectly restraining bone growth via a hypothalamic factor and at the same serving as a local autocrine/paracrine stimulator of osteoblast activity via IGF-I and an inhibitor of osteoclast generation by stimulating osteoblastic cells' antiosteoclast OPG (osteoprotegerin) expression and reducing their proosteoclast RANKL expression.
Whitfield
James F
JF
Institute for Biological Sciences, National Research Council of Canada, Ottawa, ON.
Morley
Paul
P
Willick
Gordon E
GE
D000818:Animals; D001846:Bone Development / Q000187:drug effects* / Q000502:physiology*; D003546:Cysteine Endopeptidases / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D020738:Leptin / Q000502:physiology*; D009097:Multienzyme Complexes / Q000187:drug effects; D010281:Parathyroid Hormone / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex
D015853:Cysteine Proteinase Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020738:Leptin; D009097:Multienzyme Complexes; D010281:Parathyroid Hormone; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex