title: Human migratory meniscus progenitor cells are controlled via the TGF-β pathway.
abstract: Degeneration of the knee joint during osteoarthritis often begins with meniscal lesions. Meniscectomy, previously performed extensively after meniscal injury, is now obsolete because of the inevitable osteoarthritis that occurs following this procedure. Clinically, meniscus self-renewal is well documented as long as the outer, vascularized meniscal ring remains intact. In contrast, regeneration of the inner, avascular meniscus does not occur. Here, we show that cartilage tissue harvested from the avascular inner human meniscus during the late stages of osteoarthritis harbors a unique progenitor cell population. These meniscus progenitor cells (MPCs) are clonogenic and multipotent and exhibit migratory activity. We also determined that MPCs are likely to be controlled by canonical transforming growth factor β (TGF-β) signaling that leads to an increase in SOX9 and a decrease in RUNX2, thereby enhancing the chondrogenic potential of MPC. Therefore, our work is relevant for the development of novel cell biological, regenerative therapies for meniscus repair.
authors.affiliation: Tissue Regeneration Work Group, Department of Prosthodontics, Medical Faculty, Georg-August-University, 37075 Goettingen, Germany.
authors.forename: Hayat
authors.initials: H
authors.lastname: Muhammad
authors.affiliation: Tissue Regeneration Work Group, Department of Prosthodontics, Medical Faculty, Georg-August-University, 37075 Goettingen, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Schminke
authors.affiliation: Tissue Regeneration Work Group, Department of Prosthodontics, Medical Faculty, Georg-August-University, 37075 Goettingen, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Bode
authors.affiliation: Tissue Regeneration Work Group, Department of Prosthodontics, Medical Faculty, Georg-August-University, 37075 Goettingen, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Roth
authors.affiliation: Tissue Regeneration Work Group, Department of Prosthodontics, Medical Faculty, Georg-August-University, 37075 Goettingen, Germany.
authors.forename: Julius
authors.initials: J
authors.lastname: Albert
authors.affiliation: Institute of Medical Statistics, Medical Faculty, Georg-August-University, 37075 Goettingen, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: von der Heyde
authors.affiliation: Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.
authors.forename: Vicki
authors.initials: V
authors.lastname: Rosen
authors.affiliation: Tissue Regeneration Work Group, Department of Prosthodontics, Medical Faculty, Georg-August-University, 37075 Goettingen, Germany. Electronic address: nmiosge@gwdg.de.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Miosge
mesh_terms: D000368:Aged; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008592:Menisci, Tibial / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*; D023822:Tissue Engineering / Q000379:methods; D053782:Transforming Growth Factor beta3 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D020543:Proteome; C493709:RUNX2 protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D053782:Transforming Growth Factor beta3