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Loss of p62 impairs bone turnover and inhibits PTH‐induced osteogenesis
Author(s) -
Agas Dimitrios,
Amaroli Andrea,
Lacava Giovanna,
Yanagawa Toru,
Sabbieti Maria Giovanna
Publication year - 2020
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.29654
Subject(s) - bone remodeling , parathyroid hormone , endocrinology , osteopenia , osteoblast , medicine , knockout mouse , phenotype , microbiology and biotechnology , in vitro , basal (medicine) , chemistry , biology , osteoporosis , bone mineral , receptor , calcium , biochemistry , gene , insulin
The p62 (also named sequestosome1/SQSTM1) is multidomain and multifunctional protein associated with several physiological and pathological conditions. A number of studies evidenced an involvement of p62 on the disruptive bone scenarios due to its participation in the inflammatory/osteoclastogenic pathways. However, so far, information regarding the function of p62 in the fine‐tuned processes underpinning the bone physiology are not well‐defined and are sometime discordant. We, previously, demonstrated that the intramuscular administration of a plasmid coding for p62 was able to contrast bone loss in a mouse model of osteopenia. Here, in vitro findings showed that the p62 overexpression in murine osteoblasts precursors enhanced their maturation while the p62 depletion by a specific siRNA, decreased osteoblasts differentiation. Consistently, the activity of osteoblasts from p62 −/− mice was reduced compared with wild‐type. Also, morphometric analyses of bone from p62 knockout mice revealed a pathological phenotype characterized by a lower turnover that could be explained by the poor Runx2 protein synthesis in absence of p62. Furthermore, we demonstrated that the parathyroid hormone (PTH) regulates p62 expression and that the osteogenic effects of this hormone were totally abrogated in osteoblasts from p62‐deficient mice. Therefore, these findings, for the first time, highlight the important role of p62 both for the basal and for PTH‐stimulated bone remodeling.