title: Decreased pool of mesenchymal stem cells is associated with altered chemokines serum levels in atrophic nonunion fractures.
abstract: Nonunion fractures can cause severe dysfunction and are often difficult to treat mainly due to a poor understanding of their physiopathology. Although many aspects of impaired fracture healing have been extensively studied, little is known about the cellular and molecular mechanisms leading to atrophic nonunion. Therefore, the aim of the present study was to assess the pools and biological functions of bone marrow-derived mesenchymal stem cells (hMSCs) and circulating endothelial progenitor cells (EPCs) in atrophic nonunion patients compared to healthy subjects, and the systemic levels of growth factors involved in the recruitment, proliferation and differentiation of these cells. In nonunions, the pool of hMSCs was decreased and their proliferation delayed. However, once committed, hMSCs from nonunions were able to proliferate, differentiate into osteoblastic cells and mineralize in vitro as efficiently as hMSCs from healthy subjects. In parallel, we found altered serum levels of chemokines and growth factors involved in the chemotaxis and proliferation of hMSCs such as leptin, interleukin-6 (IL-6) and its soluble receptor, platelet-derived growth factor-BB (PDGF-BB), stem cell factor (SCF) and insulin-like growth factor-1 (IGF-1). Moreover, we showed that the number of EPCs and their regulating growth factors were not affected in nonunion patients. If nonunion is generally attributed to a vascular defect, our results also support a role for a systemic mesenchymal and osteogenic cell pool defect that might be related to alterations in systemic levels of factors implicated in their chemotaxis and proliferation.
authors: Laboratory of Bone and Metabolic Biochemistry, Université Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium. myrielle.mathieu@ulb.ac.be
authors: Myrielle
authors: M
authors: Mathieu
authors: Sabrina
authors: S
authors: Rigutto
authors: Aude
authors: A
authors: Ingels
authors: Delphine
authors: D
authors: Spruyt
authors: Nadia
authors: N
authors: Stricwant
authors: Ilham
authors: I
authors: Kharroubi
authors: Valentina
authors: V
authors: Albarani
authors: Marc
authors: M
authors: Jayankura
authors: Joanne
authors: J
authors: Rasschaert
authors: Enrico
authors: E
authors: Bastianelli
authors: Valérie
authors: V
authors: Gangji
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D018925:Chemokines / Q000097:blood*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005599:Fractures, Ununited / Q000097:blood* / Q000378:metabolism*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018925:Chemokines