title: Pleiotrophin commits human bone marrow mesenchymal stromal cells towards hypertrophy during chondrogenesis.
abstract: Pleiotrophin (PTN) is a growth factor present in the extracellular matrix of the growth plate during bone development and in the callus during bone healing. Bone healing is a complicated process that recapitulates endochondral bone development and involves many cell types. Among those cells, mesenchymal stromal cells (MSC) are able to differentiate toward chondrogenic and osteoblastic lineages. We aimed to determine PTN effects on differentiation properties of human bone marrow stromal cells (hBMSC) under chondrogenic induction using histological analysis and quantitative reverse transcription polymerase chain reaction. PTN dramatically potentiated chondrogenic differentiation as indicated by a strong increase of collagen 2 protein, and cartilage-related gene expression. Moreover, PTN increased transcription of hypertrophic chondrocyte markers such as MMP13, collagen 10 and alkaline phosphatase and enhanced calcification and the content of collagen 10 protein. These effects are dependent on PTN receptors signaling and PI3 K pathway activation. These data suggest a new role of PTN in bone regeneration as an inducer of hypertrophy during chondrogenic differentiation of hBMSC.
authors: CNRS EAC 7149, CRRET Laboratory, Paris-Est University, Créteil, France ; EA3952, Cellular and Tissular Bioengineering Laboratory, Paris-Est University, Créteil, France.
authors: Thibault
authors: T
authors: Bouderlique
authors: CNRS EAC 7149, CRRET Laboratory, Paris-Est University, Créteil, France.
authors: Emilie
authors: E
authors: Henault
authors: EA3952, Cellular and Tissular Bioengineering Laboratory, Paris-Est University, Créteil, France ; Cell Therapy Facility, EFS Ile de France, Créteil, France.
authors: Angelique
authors: A
authors: Lebouvier
authors: CNRS EAC 7149, CRRET Laboratory, Paris-Est University, Créteil, France.
authors: Guilhem
authors: G
authors: Frescaline
authors: Cell Therapy Facility, EFS Ile de France, Créteil, France ; INSERM UMR955, Paris-Est University, Créteil, France.
authors: Phillipe
authors: P
authors: Bierling
authors: EA3952, Cellular and Tissular Bioengineering Laboratory, Paris-Est University, Créteil, France ; Cell Therapy Facility, EFS Ile de France, Créteil, France.
authors: Helene
authors: H
authors: Rouard
authors: CNRS EAC 7149, CRRET Laboratory, Paris-Est University, Créteil, France.
authors: José
authors: J
authors: Courty
authors: CNRS EAC 7149, CRRET Laboratory, Paris-Est University, Créteil, France.
authors: Patricia
authors: P
authors: Albanese
authors: EA3952, Cellular and Tissular Bioengineering Laboratory, Paris-Est University, Créteil, France ; Cell Therapy Facility, EFS Ile de France, Créteil, France.
authors: Nathalie
authors: N
authors: Chevallier
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D049108:Cell Enlargement; D020219:Chondrogenesis / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; C066845:pleiotrophin