title: Signature of microRNA expression during osteogenic differentiation of bone marrow MSCs reveals a putative role of miR-335-5p in osteoarthritis.
abstract: BACKGROUND
  The aim of this study was to evaluate, the existence of a signature of differentially expressed microRNAs (miRNAs) during osteogenic differentiation of bone marrow MSCs from OA and healthy donors and to describe their possible implication in joint regeneration through modulation of molecular mechanisms involved in homeostatic control in OA pathophysiology.
  
  
  METHODS
  Following phenotypic assessment of BM-MSCs obtained from OA diagnosed patients (n = 10) and non-OA (n = 10), total small RNA was isolated after osteogenic induction for 1, 10 and 21 days, miRNA profiles were generated using a commercial expression array of 754 well-characterized miRNAs. MiRNAs, with consistent differential expression were selected for further validation by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis.
  
  
  RESULTS
  A total of 246 miRNAs were differentially expressed (fold change ≥ ± 2, P ≤0.05) between OA and non-OA BM-MSC samples; these miRNAs showed variable interactions depending on the cell and differentiation status. Two miRNAs, hsa-miR-210 and hsa-miR-335-5p out of 21 used for validation showed a significant downregulated expression during induced osteogenesis. In particular hsa-miR-335-5p, a critical regulator in bone homeostasis, was further studied. hsa-miR-335-5p downregulation in OA-MSCs, as well as their host coding gene, MEST, were also assessed.
  
  
  CONCLUSIONS
  To our knowledge, this study represents the most comprehensive assessment to date of miRNA expression profiling in BM-MSCs from OA patients and their role during osteogenic differentiation. We describe the existence of a correlation between miR-335-5p expression and OA indicating the putative role of this miRNA in OA features. These findings, may contribute to our understanding of the molecular mechanisms involved in MSCs mediated homeostatic control in OA pathophysiology that could be applicable in future therapeutic approaches.
authors.affiliation: Rheumatology Service, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC). UGC de Reumatología, Hospital Clínico San Carlos, 4a Planta, Ala Norte. C/ Profesor Martín Lagos s/n, 28040, Madrid, Spain. mptornero@gmail.com.
authors.forename: Pilar
authors.initials: P
authors.lastname: Tornero-Esteban
authors.affiliation: Rheumatology Service, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC). UGC de Reumatología, Hospital Clínico San Carlos, 4a Planta, Ala Norte. C/ Profesor Martín Lagos s/n, 28040, Madrid, Spain. lrodriguezr.hcsc@salud.madrid.org.
authors.forename: Luis
authors.initials: L
authors.lastname: Rodríguez-Rodríguez
authors.affiliation: Rheumatology Service, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC). UGC de Reumatología, Hospital Clínico San Carlos, 4a Planta, Ala Norte. C/ Profesor Martín Lagos s/n, 28040, Madrid, Spain. lydia.abasolo@salud.madrid.org.
authors.forename: Lydia
authors.initials: L
authors.lastname: Abásolo
authors.affiliation: Department of Regenerative Cardiology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain. mtome@cnb.csic.es.
authors.forename: María
authors.initials: M
authors.lastname: Tomé
authors.affiliation: Department of Regenerative Cardiology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain. plromero1@gmail.com.
authors.forename: Pedro
authors.initials: P
authors.lastname: López-Romero
authors.affiliation: Rheumatology Service, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC). UGC de Reumatología, Hospital Clínico San Carlos, 4a Planta, Ala Norte. C/ Profesor Martín Lagos s/n, 28040, Madrid, Spain. evaherranzdlp@hotmail.com.
authors.forename: Eva
authors.initials: E
authors.lastname: Herranz
authors.affiliation: Department of Regenerative Cardiology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain. maglez75@hotmail.com.
authors.forename: Manuel A
authors.initials: MA
authors.lastname: González
authors.affiliation: Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC). UGC de Traumatología, Hospital Clínico San Carlos, Madrid, Spain. fmarco@med.ucm.es.
authors.forename: Fernando
authors.initials: F
authors.lastname: Marco
authors.affiliation: Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC). UGC de Traumatología, Hospital Clínico San Carlos, Madrid, Spain. enrmoro@hotmail.com.
authors.forename: Enrique
authors.initials: E
authors.lastname: Moro
authors.affiliation: Rheumatology Service, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC). UGC de Reumatología, Hospital Clínico San Carlos, 4a Planta, Ala Norte. C/ Profesor Martín Lagos s/n, 28040, Madrid, Spain. benjamin.fernandez@salud.madrid.org.
authors.forename: Benjamín
authors.initials: B
authors.lastname: Fernández-Gutiérrez
authors.affiliation: Rheumatology Service, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC). UGC de Reumatología, Hospital Clínico San Carlos, 4a Planta, Ala Norte. C/ Profesor Martín Lagos s/n, 28040, Madrid, Spain. jrlamas@gmail.com.
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Lamas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D035683:MicroRNAs / Q000096:biosynthesis*; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D010012:Osteogenesis / Q000502:physiology*
chemical_list: C556347:MIRN335 microRNA, human; D035683:MicroRNAs