title: The role of the progressive ankylosis protein (ANK) in adipogenic/osteogenic fate decision of precursor cells.
abstract: The progressive ankylosis protein (ANK) is a transmembrane protein that transports intracellular pyrophosphate (PPi) to the extracellular milieu. In this study we show increased fatty degeneration of the bone marrow of adult ank/ank mice, which lack a functional ANK protein. In addition, isolated bone marrow stromal cells (BMSCs) isolated from ank/ank mice showed a decreased proliferation rate and osteogenic differentiation potential, and an increased adipogenic differentiation potential compared to BMSCs isolated from wild type (WT) littermates. Wnt signaling pathway PCR array analysis revealed that Wnt ligands, Wnt receptors and Wnt signaling proteins that stimulate osteoblast differentiation were expressed at markedly lower levels in ank/ank BMSCs than in WT BMSCs. Lack of ANK function also resulted in impaired bone fracture healing, as indicated by a smaller callus formed and delayed bone formation in the callus site. Whereas 5weeks after fracture, the fractured bone in WT mice was further remodeled and restored to original shape, the fractured bone in ank/ank mice was not fully restored and remodeled to original shape. In conclusion, our study provides evidence that ANK plays a critical role in the adipogenic/osteogenic fate decision of adult mesenchymal precursor cells. ANK functions in precursor cells are required for osteogenic differentiation of these cells during adult bone homeostasis and repair, whereas lack of ANK functions favors adipogenic differentiation.
authors.affiliation: Musculoskeletal Research Center, Department of Orthopaedic Surgery, New York University School of Medicine, NY, New York, United States.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Minashima
authors.affiliation: Musculoskeletal Research Center, Department of Orthopaedic Surgery, New York University School of Medicine, NY, New York, United States.
authors.forename: Martin
authors.initials: M
authors.lastname: Quirno
authors.affiliation: Musculoskeletal Research Center, Department of Orthopaedic Surgery, New York University School of Medicine, NY, New York, United States.
authors.forename: You Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Musculoskeletal Research Center, Department of Orthopaedic Surgery, New York University School of Medicine, NY, New York, United States. Electronic address: thorsten.kirsch@nyumc.org.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kirsch
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology*; D005260:Female; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008817:Mice, Mutant Strains; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D028061:Phosphate Transport Proteins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D060449:Wnt Signaling Pathway / Q000502:physiology; D055114:X-Ray Microtomography
chemical_list: D028061:Phosphate Transport Proteins; C410982:ank protein, mouse
keywords: Adipogenesis; Bone fracture healing; Osteogenesis; Progressive ankylosis protein (ANK); Wnt/β-catenin signaling