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P62 deficiency shifts mesenchymal/stromal stem cell commitment toward adipogenesis and disrupts bone marrow homeostasis in aged mice
Author(s) -
Lacava Giovanna,
Laus Fulvio,
Amaroli Andrea,
Marchegiani Andrea,
Censi Roberta,
Di Martino Piera,
Yanagawa Toru,
Sabbieti Maria Giovanna,
Agas Dimitrios
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28299
Subject(s) - mesenchymal stem cell , bone marrow , stromal cell , haematopoiesis , stem cell , adipogenesis , microbiology and biotechnology , biology , osteopenia , bone remodeling , homeostasis , hematopoietic stem cell , immunology , endocrinology , cancer research , osteoporosis , bone mineral
With advancing age have been observed bone and bone marrow phenotypic alterations due to the impaired bone tissue homeostatic features, involving bone remodeling, and bone marrow niche ontogeny. The complex “inflamm‐aging” pathological scenario that culminates with osteopenia and mesenchymal/stromal and hematopoietic stem cell commitment breakdown, is controlled by cellular and molecular intramural components comprising adapter proteins such as the sequestosome 1 (p62/SQSTM1). p62, a “multiway function” protein, has been reported as an effective anti‐inflammatory, bone‐building factor. In this view, we considered for the first time the involvement of p62 in aging bone and bone marrow of 1 year and 2 years p62 −/− mice. Interestingly, p62 deficiency provoked accelerated osteopenia and impaired niche operational activities within the bone marrow. The above findings unearthed the importance of p62 in mesenchymal stem cell maintenance/differentiation schedule in old animals and provide, at least in part, a mechanistic scenario of p62 action.