title: Functionally deficient mesenchymal stem cells reside in the bone marrow niche with M2-macrophages and amyloid-β protein adjacent to loose total joint implants.
abstract: We sought to demonstrate whether there is a difference in the local mesenchymal stem cells (MSC) niche obtained from patients undergoing their first total joint replacement surgery versus those patients undergoing a revision surgery for an failing total joint implant. Bone marrow aspirates collected from patients undergoing revision total joint arthroplasty were observed to be less clonal and the expression of PDGFRα, CD51, ALCAM, endoglin, CXCL12, nestin, and nucleostemin were decreased. Revision MSC were also less able to commit to an osteoblast-lineage or an adipocyte-lineage. Further, in revision MSC, OPG, and IL6 expression were increased. Monocytes, derived from revision whole marrow aspirates, were less capable of differentiating into osteoclasts, the cells implicated in the pathologic degradation of bone. Osteoclasts were also not observed in tissue samples collected adjacent to the implants of revision patients; however, the alternatatively activated M2-macrophage phenotype was observed in parallel with pathologic accumulations of amyloid-β, τ-protien and 3-nitrotyrosine. Despite the limited numbers of patients examined, our data suggest that nucleostemin may be a useful functional marker for MSC while the observation of M2-macrophage infiltration around the implant lays the foundation for future investigation into a novel mechanism that we propose is associated with loose total joint implants.
authors.affiliation: Department of Orthopedic Surgery, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Bryan S
authors.initials: BS
authors.lastname: Margulies
authors.forename: Sean D
authors.initials: SD
authors.lastname: DeBoyace
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Parsons
authors.forename: Connor G
authors.initials: CG
authors.lastname: Policastro
authors.forename: Jessica S S
authors.initials: JS
authors.lastname: Ee
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Damron
mesh_terms: D000368:Aged; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D019643:Arthroplasty, Replacement; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism*; D005269:Femur / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008264:Macrophages; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008875:Middle Aged; D010012:Osteogenesis; D011475:Prosthesis Failure; D012086:Reoperation; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D016875:tau Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine
keywords: bone marrow; mesenchymal stem cells; monocyte; myeloid cells; osteoblast