title: Comprehensive profiling analysis of actively resorbing osteoclasts identifies critical signaling pathways regulated by bone substrate.
abstract: As the only cells capable of efficiently resorbing bone, osteoclasts are central mediators of both normal bone remodeling and pathologies associates with excessive bone resorption. However, despite the clear evidence of interplay between osteoclasts and the bone surface in vivo, the role of the bone substrate in regulating osteoclast differentiation and activation at a molecular level has not been fully defined. Here, we present the first comprehensive expression profiles of osteoclasts differentiated on authentic resorbable bone substrates. This analysis has identified numerous critical pathways coordinately regulated by osteoclastogenic cytokines and bone substrate, including the transition from proliferation to differentiation, and sphingosine-1-phosphate signaling. Whilst, as expected, much of this program is dependent upon integrin beta 3, the pre-eminent mediator of osteoclast-bone interaction, a surprisingly significant portion of the bone substrate regulated expression signature is independent of this receptor. Together, these findings identify an important hitherto underappreciated role for bone substrate in osteoclastogenesis.
authors.affiliation: Hospital for Special Surgery, New York, NY 10021.
authors.forename: P Edward
authors.initials: PE
authors.lastname: Purdue
authors.affiliation: 1] School of Medical Sciences, The University of Adelaide, Adelaide 5005, Australia [2] Beth Israel Deaconess Medical Center, Boston, MA 02215.
authors.forename: Tania N
authors.initials: TN
authors.lastname: Crotti
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215.
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, 06877.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Swantek
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, 06877.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, 06877.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hill
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, 06877.
authors.forename: Adedayo
authors.initials: A
authors.lastname: Hanidu
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, 06877.
authors.forename: Janice
authors.initials: J
authors.lastname: Dimock
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, 06877.
authors.forename: Gerald
authors.initials: G
authors.lastname: Nabozny
authors.affiliation: Hospital for Special Surgery, New York, NY 10021.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldring
authors.affiliation: University of Florida College of Dentistry, Gainesville, FL, 32610.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: McHugh
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*