title: In vitroBMP2 stimulation of osteoblast citrate production in concert with mineralized bone nodule formation.
abstract: BACKGROUND
  That citrate is a major indispensible component of bone in humans and in all osteovertebrates has been known for about seventy-five years. Yet, its role and importance in the structure and function of bone and bone formation have remained unknown. However, recent studies have identified that citrate is a major and essential component of the apatite/collagen structure of bone; and that the biomechanical properties of bone (e.g., stability, strength, resistance to fracture) depend on the appropriate incorporation of citrate in the structure of bone. The osteoblasts have recently been identified as citrate-producing cells that provide the citrate that is incorporated in the apatite/collagen structure during osteogenesis. Little is known regarding the factors and mechanisms involved in the regulation of citrate that is incorporated along with mineralization during the process of bone formation. Because of the importance of BMP2 in the initiation of osteogenesis and the development of the osteoblasts, it is essential to determine its possible implication in the development of the citrate-producing capability of the osteoblasts (i.e., "citration") during the formation of mineralized bone nodules.
  
  
  METHODS
  The goal of this study was to determine if BMP2 promotes the development of citrate-producing osteoblasts for increased citrate incorporation in the formation of mineralized bone nodules. The study employed MC3T3 mesenchyme stem cell osteogenic differentiation in the presence and absence of BMP2.
  
  
  RESULTS
  The results showed that BMP2 treatment increased the osteogenic development of mineralized bone nodules. In addition, BMP2 increased osteoblast citrate production and incorporation in the mineralized bone nodule. This was accompanied by increased ZIP1 transporter, which is an essential genetic/metabolic event for citrate-producing cells.
  
  
  CONCLUSIONS
  The results demonstrate, for the first time, that BMP2 facilitates the osteoblast "citration" process in concert with mineralization during bone formation; and provide confirmation of the important role of osteoblasts as specialized citrate-producing cells in the process of bone formation. However, it is essential to determine if thesein vitroeffects will occurin vivoin BMP2-implant induction of bone formation. "Citration" is essential for osteoinductive bone to represent the chemical, structural, and biomechanical properties of "normal" bone.
authors.affiliation: Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, USA.
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Costello
authors.affiliation: Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, USA.
authors.forename: Meenakshi A
authors.initials: MA
authors.lastname: Chellaiah
authors.affiliation: Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Periodontics, Dental School, University of Maryland, Baltimore, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Reynolds
authors.affiliation: Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, USA.
authors.forename: Renty B
authors.initials: RB
authors.lastname: Franklin
keywords: BMP2; ZIP1 transporter; apatite/collagen complex; citrate production; citration and mineralization; mesenchyme stem cells; mineralized bone formation; osteoblasts; osteogenesis