REVIEW Adipocytes and the Regulation of Bone Remodeling: A Balancing Act Mark E. Nuttall • Forum Shah • Vikramjeet Singh • Caasy Thomas-Porch • Trivia Frazier • Jeffrey M. Gimble Received: 10 April 2013 / Accepted: 12 September 2013 / Published online: 8 October 2013 Ó Springer Science+Business Media New York 2013 Abstract Throughout life, a balance exists within the marrow cavity between adipose tissue and bone. Each tissue derives from a common progenitor cell known both as a ‘‘bone marrow-derived multipotent stromal cell’’ and as a ‘‘mesenchymal stem cell’’ (BMSC). The majority of in vitro and in vivo data suggest that BMSCs differentiate into adipocytes or osteoblasts in a reciprocal manner. For example, while ligand induction of the transcription factors peroxisome proliferator-activated receptor c initiates BMSC adipogenesis, it suppresses osteogenesis. Never- theless, this hypothesis may oversimplify a complex reg- ulatory paradigm. The picture may be further complicated by the systemic impact of extramedullary adipose depots on bone via the secretion of protein adipokines and lipid metabolites. This review focuses on past and current lit- erature examining the mechanisms governing the adipose– bone interface. Keywords Adipocyte Á Bone marrow cell Á Gene transcription regulation Á Mesenchymal stem cell Á Osteoblast Introduction Homeostatic mechanisms play a fundamental role in defining bone metabolism and physiology. While the his- toric focus had been on the homeostatic balance between bone growth and remodeling, research during the past two decades has broadened the homeostatic concept to encompass the balance between adipose depots and bone. In their pioneering 1992 publication, Beresford et al. [1] introduced the hypothesis that bone marrow mesenchymal stromal/stem cell (BMSC) differentiation along the adipo- cyte and osteoblast lineage pathways displayed a reciprocal relationship. Although a wealth of supporting data have evolved during the intervening years, the relationship between adipose tissues and bone is more complex than a simple ‘‘either/or’’ decision point [2–5]. The current review will explore the balance between adipose tissue and bone Jeffrey M. Gimble is the co-founder and Chief Scientific Officer of LaCell LLC and is co-inventor on multiple patents relating to the use of adipose-derived cells and materials for regenerative medicine. All other authors have stated that they have no conflict of interest. M. E. Nuttall (&) Janssen Pharmaceuticals, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USA e-mail: nnuttall@its.jnj.com F. Shah Á V. Singh Á C. Thomas-Porch Á T. Frazier Á J. M. Gimble Stem Cell Biology Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA C. Thomas-Porch Department of Biomedical Sciences, Tulane University School of Medicine, New Orleans, LA 70112, USA J. M. Gimble (&) Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, 1324 Tulane Avenue SL-99, New Orleans, LA 70112, USA e-mail: jgimble@tulane.edu J. M. Gimble Department of Orthopaedic Surgery, Louisiana State University Health Science Center, New Orleans, LA 70112, USA 123 Calcif Tissue Int (2014) 94:78–87 DOI 10.1007/s00223-013-9807-6