title: An investigation of BMP-7 mediated alterations to BMP signalling components in human tenocyte-like cells.
abstract: The incidence of tendon re-tears post-surgery is an ever present complication. It is suggested that the application of biological factors, such as bone morphogenetic protein 7 (BMP-7), can reduce complication rates by promoting tenogenic characteristics in in vitro studies. However, there remains a dearth of information in regards to the mechanisms of BMP-7 signalling in tenocytes. Using primary human tenocyte-like cells (hTLCs) from the supraspinatus tendon the BMP-7 signalling pathway was investigated: induction of the BMP associated Smad pathway and non-Smad pathways (AKT, p38, ERK1/2 and JNK); alterations in gene expression of BMP-7 associated receptors, Smad pathway components, Smad target gene (ID1) and tenogenic marker scleraxis. BMP-7 increases the expression of specific BMP associated receptors, BMPR-Ib and BMPR-II, and Smad8. Additionally, BMP-7 activates significantly Smad1/5/8 and slightly p38 pathways as indicated by an increase in phosphorylation and proven by inhibition experiments, where p-ERK1/2 and p-JNK pathways remain mainly unresponsive. Furthermore, BMP-7 increases the expression of the Smad target gene ID1, and the tendon specific transcription factor scleraxis. The study shows that tenocyte-like cells undergo primarily Smad8 and p38 signalling after BMP-7 stimulation. The up-regulation of tendon related marker genes and matrix proteins such as Smad8/9, scleraxis and collagen I might lead to positive effects of BMP-7 treatment for rotator cuff repair, without significant induction of osteogenic and chondrogenic markers.
authors.affiliation: Julius Wolff Institute, Charité-Universitaetsmedizin Berlin, Germany.|Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitaetsmedizin Berlin, Germany.
authors.forename: Franka
authors.initials: F
authors.lastname: Klatte-Schulz
authors.affiliation: Julius Wolff Institute, Charité-Universitaetsmedizin Berlin, Germany.|Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitaetsmedizin Berlin, Germany.
authors.forename: Gerry
authors.initials: G
authors.lastname: Giese
authors.affiliation: Julius Wolff Institute, Charité-Universitaetsmedizin Berlin, Germany.|Berlin-Brandenburg School for Regenerative Therapies, Charité-Universitaetsmedizin Berlin, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Differ
authors.affiliation: Julius Wolff Institute, Charité-Universitaetsmedizin Berlin, Germany.|Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitaetsmedizin Berlin, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Minkwitz
authors.affiliation: Institute for Chemistry and Biochemistry, Freie Universitaet Berlin, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Ruschke
authors.affiliation: Julius Wolff Institute, Charité-Universitaetsmedizin Berlin, Germany.|Berlin-Brandenburg School for Regenerative Therapies, Charité-Universitaetsmedizin Berlin, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Puts
authors.affiliation: Berlin-Brandenburg School for Regenerative Therapies, Charité-Universitaetsmedizin Berlin, Germany.|Institute for Chemistry and Biochemistry, Freie Universitaet Berlin, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Knaus
authors.affiliation: Julius Wolff Institute, Charité-Universitaetsmedizin Berlin, Germany.|Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitaetsmedizin Berlin, Germany.
authors.forename: Britt
authors.initials: B
authors.lastname: Wildemann
mesh_terms: D000368:Aged; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000502:physiology*; D013710:Tendons / Q000166:cytology / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D016326:Extracellular Matrix Proteins