title: Mesenchymal stem cell proliferation and mineralization but not osteogenic differentiation are strongly affected by extracellular pH.
abstract: Osteomyelitis is a serious complication in oral and maxillofacial surgery affecting bone healing. Bone remodeling is not only controlled by cellular components but also by ionic and molecular composition of the extracellular fluids in which calcium phosphate salts are precipitated in a pH dependent manner.
  
  
  OBJECTIVE
  To determine the effect of pH on self-renewal, osteogenic differentiation and matrix mineralization of mesenchymal stem cells (MSCs).
  
  
  METHODS
  We selected three different pH values; acidic (6.3, 6.7), physiological (7.0-8.0) and severe alkaline (8.5). MSCs were cultured at different pH ranges, cell viability measured by WST-1, apoptosis detected by JC-1, senescence was analyzed by β-galactosidase whereas mineralization was detected by Alizarin Red and osteogenic differentiation analyzed by Real-time PCR.
  
  
  RESULTS
  Self-renewal was affected by pH as well as matrix mineralization in which pH other than physiologic inhibited the deposition of extracellular matrix but did not affect MSCs differentiation as osteoblast markers were upregulated. The expression of osteocalcin and alkaline phosphatase activity was upregulated whereas osteopontin was downregulated under acidic pH.
  
  
  CONCLUSIONS
  pH affected MSCs self-renewal and mineralization without influencing osteogenic differentiation. Thus, future therapies, based on shifting acid-base balance toward the alkaline direction might be beneficial for prevention or treatment of osteomyelitis.
authors.affiliation: Experimental Surgery and Regenerative Medicine, Ludwig-Maximilians-University, Munich, Germany; Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University, Munich, Germany; Department of Oral and Maxillofacial Surgery, Alexandria-University, Alexandria, Egypt. Electronic address: Riham.Fliefel@med.uni-muenchen.de.
authors.forename: Riham
authors.initials: R
authors.lastname: Fliefel
authors.affiliation: Experimental Surgery and Regenerative Medicine, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Cvetan
authors.initials: C
authors.lastname: Popov
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Tröltzsch
authors.affiliation: Department of Conservative Dentistry and Periodontology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Kühnisch
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ehrenfeld
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Otto
mesh_terms: D017209:Apoptosis; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
keywords: MSCs; Mineralization; Osteogenic differentiation; Osteomyelitis; Proliferation; pH