title: Periostin secreted by mesenchymal stem cells supports tendon formation in an ectopic mouse model.
abstract: True tendon regeneration in human patients remains a vision of musculoskeletal therapies. In comparison to other mesenchymal lineages the biology of tenogenic differentiation is barely understood. Specifically, easy and efficient protocols are lacking that might enable tendon cell and tissue differentiation based on adult (stem) cell sources. In the murine mesenchymal progenitor cell line C3H10T½, overexpression of the growth factor bone morphogenetic protein 2 (BMP2) and a constitutively active transcription factor, Smad8 L+MH2, mediates tendon cell differentiation in vitro and the formation of tendon-like tissue in vivo. We hypothesized that during this differentiation secreted factors involved in extracellular matrix formation exert a major impact on tendon development. Gene expression analyses revealed four genes encoding secreted factors that are notably upregulated: periostin, C-type lectin domain family 3 (member b), RNase A4, and follistatin-like 1. These factors have not previously been implicated in tendon biology. Among these, periostin showed a specific expression in tenocytes of adult mouse Achilles tendon and in chondrocytes within the nonmineralized fibrocartilage zone of the enthesis with the calcaneus. Overexpression of periostin alone or in combination with constitutively active BMP receptor type in human mesenchymal stem cells and subsequent implantation into ectopic sites in mice demonstrated a reproducible moderate tenogenic capacity that has not been described before. Therefore, periostin may belong to the factors contributing to the development of tenogenic tissue.
authors.affiliation: 1 Department of Orthopaedic Trauma, Hannover Medical School (MHH), Hannover, Germany .
authors.forename: Sandra
authors.initials: S
authors.lastname: Noack
authors.forename: Virginia
authors.initials: V
authors.lastname: Seiffart
authors.forename: Elmar
authors.initials: E
authors.lastname: Willbold
authors.forename: Sandra
authors.initials: S
authors.lastname: Laggies
authors.forename: Andreas
authors.initials: A
authors.lastname: Winkel
authors.forename: Sandra
authors.initials: S
authors.lastname: Shahab-Osterloh
authors.forename: Thilo
authors.initials: T
authors.lastname: Flörkemeier
authors.forename: Falk
authors.initials: F
authors.lastname: Hertwig
authors.forename: Christine
authors.initials: C
authors.lastname: Steinhoff
authors.forename: Ulrike A
authors.initials: UA
authors.lastname: Nuber
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gross
authors.forename: Andrea
authors.initials: A
authors.lastname: Hoffmann
mesh_terms: D000125:Achilles Tendon / Q000503:physiopathology*; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D005260:Female; D038702:Follistatin-Related Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008819:Mice, Nude; D012038:Regeneration; D015854:Up-Regulation
chemical_list: D015815:Cell Adhesion Molecules; D038702:Follistatin-Related Proteins; D037181:Lectins, C-Type; C512835:POSTN protein, human; C048648:tetranectin; C448799:FSTL1 protein, human; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease