Abstract
BackgroundThe 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.MethodsFollowing 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.ResultsA 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.ConclusionsTo 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-015-0652-9) contains supplementary material, which is available to authorized users.
Highlights
The aim of this study was to evaluate, the existence of a signature of differentially expressed microRNAs 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
To describe the role of miRNAs in OA pathophysiology, we aimed to evaluate the existence of a differential expression signature of miRNAs in bone marrow MSCs comparing OA and healthy donors during in vitro induced osteogenesis
Characterization of bone marrow MSCs The phenotypic uniformity of Bone marrow mesenchymal stem cells (BM-MSCs) used in the study was assessed according to several minimal criteria: these include the plastic-adherence in culture, positivity for expression of CD90, CD73, CD105 and absence of hematopoietic surface markers CD34, CD45 and CD14 expression and their osteogenic and chondrogenic lineage potential
Summary
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. Osteoarthritis (OA) is a common musculoskeletal disorder with high socioeconomic impact [1] It is characterized by alterations in bone-cartilage homeostasis leading to progressive degeneration of synovial joints [2]. No cure exists for OA, beyond pain relief In this context, cell therapies are being studied as an alternative for OA treatment [5]. Therapeutic approaches using MSCs (Mesenchymal Stem in Cells) are considered one of the best options for future treatment of damaged OA cartilage and bone. This approach is based on the potential of MSCs to differentiate into chondrocytes and osteoblasts and their immunomodulatory properties
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