title: Mesenchymal stem cell transplantation in tight-skin mice identifies miR-151-5p as a therapeutic target for systemic sclerosis.
abstract: Systemic sclerosis (SSc), an autoimmune disease, may cause significant osteopenia due to activation of the IL4Rα/mTOR pathway. Mesenchymal stem cell transplantation (MSCT) can ameliorate immune disorders in SSc via inducing immune tolerance. However, it is unknown whether MSCT rescues osteopenia phenotype in SSc. Here we show that MSCT can effectively ameliorate osteopenia in SSc mice by rescuing impaired lineage differentiation of the recipient bone marrow MSCs. Mechanistically, we show that donor MSCs transfer miR-151-5p to the recipient bone marrow MSCs in SSc mice to inhibit IL4Rα expression, thus downregulating mTOR pathway activation to enhance osteogenic differentiation and reduce adipogenic differentiation. Moreover, systemic delivery of miR-151-5p is capable of rescuing osteopenia, impaired bone marrow MSCs, tight skin, and immune disorders in SSc mice, suggesting that miR-151-5p may be a specific target for SSc treatment. Our finding identifies a previously unrecognized role of MSCT in transferring miRNAs to recipient stem cells to ameliorate osteopenia via rescuing a non-coding RNA pathway.
authors.affiliation: Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA 19104, USA.
authors.forename: Chider
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu 210008, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Division of Advanced Prosthodontics, Weintraub Center for Reconstructive Biotechnology, School of Dentistry, University of California, Los Angeles, CA 90095, USA.
authors.forename: Alireza
authors.initials: A
authors.lastname: Moshaverinia
authors.affiliation: Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA 19104, USA.
authors.forename: Dawei
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA 19104, USA.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Kou
authors.affiliation: Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA 19104, USA.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA 19104, USA.
authors.forename: Ruili
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu 210008, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA 19104, USA.
authors.forename: Songtao
authors.initials: S
authors.lastname: Shi
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000473:pathology / Q000628:therapy; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D055354:Exosomes / Q000378:metabolism; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D010012:Osteogenesis; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000378:metabolism; D019948:Receptors, Interleukin-4 / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000097:blood / Q000235:genetics* / Q000628:therapy*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C582434:MIRN151 microRNA, mouse; C548886:MIRN151a microRNA, human; D035683:MicroRNAs; D019948:Receptors, Interleukin-4; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase; D058570:TOR Serine-Threonine Kinases