Autophagy in bone homeostasis and the onset of osteoporosis

Yin, Xing; Zhou, Chenchen; Li, Jingtao; Liu, Renkai; Shi, Bing; Yuan, Quan; Zou, Shujuan

doi:10.1038/s41413-019-0058-7

Cited by 162 publications

(154 citation statements)

References 223 publications

(269 reference statements)

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“…Under normal conditions, there is a sharp equilibrium between bone formation and resorption and its disruption can lead to pathological conditions [ 25 ]. This dynamic balance can be influenced by hormones, growth factors, and mechanical impulses as extrinsic factors and autophagy as an intrinsic one [ 16 , 25 , 26 ].…”

Section: Bone Remodelingmentioning

confidence: 99%

The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function

et al. 2020

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Autophagy is an evolutionary conserved and highly regulated recycling process of cellular wastes. Having a housekeeping role, autophagy through the digestion of domestic cytosolic organelles, proteins, macromolecules, and pathogens, eliminates unnecessary materials and provides nutrients and energy for cell survival and maintenance. The critical role of autophagy and autophagy-related proteins in osteoclast differentiation, bone resorption, and maintenance of bone homeostasis has previously been reported. Increasing evidence reveals that autophagy dysregulation leads to alteration of osteoclast function and enhanced bone loss, which is associated with the onset and progression of osteoporosis. In this review, we briefly consolidate the current state-of-the-art technology regarding the role of autophagy in osteoclast function in both physiologic and pathologic conditions to have a more general view on this issue.

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Section: Bone Remodelingmentioning

confidence: 99%

The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function

et al. 2020

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“…Among proteins expected to interact with ATG8, such as ATG3 and ATG7, the mammalian homolog of the mammalian cargo receptor NBR1, SmNBR1, was identified as an interaction partner of SmATG8 (Werner et al 2019). In mammals, NBR1 is a ubiquitously expressed conserved protein that is associated with signaling pathways and bone metabolism (Yin et al 2019). It was also described as a binding partner of Atg8 family proteins where it acts as a receptor that mediates the docking of ubiquitinated substrates to the autophagosomal membrane protein LC3/ ATG8 (Kirkin et al 2009;Lamark et al 2009).…”

Section: Analysis Of Developmental Mutants Reveals the Role Of Multi-mentioning

confidence: 99%

Sordaria macrospora: 25 years as a model organism for studying the molecular mechanisms of fruiting body development

Teichert

Pöggeler

Nowrousian

2020

Appl Microbiol Biotechnol

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Fruiting bodies are among the most complex multicellular structures formed by fungi, and the molecular mechanisms that regulate their development are far from understood. However, studies with a number of fungal model organisms have started to shed light on this developmental process. One of these model organisms is Sordaria macrospora, a filamentous ascomycete from the order Sordariales. This fungus has been a genetic model organism since the 1950s, but its career as a model organism for molecular genetics really took off in the 1990s, when the establishment of a transformation protocol, a mutant collection, and an indexed cosmid library provided the methods and resources to start revealing the molecular mechanisms of fruiting body development. In the 2000s, "omics" methods were added to the S. macrospora tool box, and by 2020, 58 developmental genes have been identified in this fungus. This review gives a brief overview of major method developments for S. macrospora, and then focuses on recent results characterizing different processes involved in regulating development including several regulatory protein complexes, autophagy, transcriptional and chromatin regulation, and RNA editing. Key points •Sordaria macrospora is a model system for analyzing fungal fruiting body development. •More than 100 developmental mutants are available for S. macrospora. •More than 50 developmental genes have been characterized in S. macrospora.

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“…(37,38) It also is involved in carcinogenesis and metastasis, (69) cell replication, and autophagy, which plays central roles in bone homeostasis through effects on ostb, osteocytes, and osteoclasts. (70) HMGA2 displays very low or negligible expression in normal postnatal tissues but is highly expressed in some mesoderm-derived stem or progenitor cell types including MSC, myob, and preadipocytes. It is much more weakly expressed in ostb, in accord with its negative effects on ostb formation from MSC.…”

Section: Npr3 (Nprc) One Of the Tier-1 Snp Associated Genes Is Invomentioning

confidence: 99%

“…(71) Besides a role for HMGA2 in negatively regulating MSC differentiation to ostb, it may play a protective role in the skeleton (73) at later steps in differentiation of ostb to osteocytes and in osteocyte homeostasis by helping to induce autophagy. (70,74,75) Like our five osteoporosis-risk candidate genes, the TFs predicted to bind to the Tier-1 SNPcontaining DNA sequences associated with these genes have special functions in the skeletal system (Supplemental Table S6). Further evidence implicating Tier-1 SNPs as transcription-regulatory variants comes from our finding that 11 of the 16 SNPs for BICC1, DAAM2, or NPR3 overlapped eQTLs for one or several tissues in which these genes are expressed.…”

Section: Npr3 (Nprc) One Of the Tier-1 Snp Associated Genes Is Invomentioning

confidence: 99%

Prioritization of osteoporosis-associated GWAS SNPs using epigenomics and transcriptomics

Zhang

Deng

Shen

et al. 2020

Preprint

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Genetic risk factors for osteoporosis, a prevalent disease associated with aging, have been examined in many genome-wide association studies (GWAS). A major challenge is to prioritize transcription-regulatory GWAS-derived variants that are likely to be functional. Given the critical role of epigenetics in gene regulation, we have used an unusual epigenetics-and transcription-based approach to identify credible regulatory SNPs relevant to osteoporosis from 38 reported BMD GWAS. Using Roadmap databases, we prioritized SNPs based upon their overlap with strong enhancer or promoter chromatin preferentially in osteoblasts relative to 11 heterologous cell culture types. The selected SNPs also had to overlap open chromatin (DNaseI-hypersensitive sites) and DNA sequences predicted to bind to osteoblast-relevant transcription factors in an allele-specific manner. From >50,000 GWAS-derived SNPs, we identified 16 novel and credible regulatory SNPs (Tier-1 SNPs) for osteoporosis risk. Their associated genes, BICC1, LGR4, DAAM2, NPR3, or HMGA2, are involved in osteoblastogenesis or bone homeostasis and regulate cell signaling or enhancer function. Four of them are preferentially expressed in osteoblasts. BICC1, LGR4, and DAAM2 play important roles in canonical Wnt signaling, a pathway critical to bone formation and repair. The transcription factors that are predicted to bind to the Tier-1 SNP-containing DNA sequences also have bone-related functions. For the seven Tier-1 SNPs near the 5' end of BICC1, examination of eQTL overlap and the distribution of BMD-increasing alleles suggests that at least one SNP in each of two clusters contributes to inherited osteoporosis risk. Our study not only illustrates a method that can be used to identify novel BMD-related causal regulatory SNPs for future study, but also reveals evidence that some of the Tier-1 SNPs exert their effects on BMD risk indirectly through little-studied noncoding RNA genes, which in turn may control the nearby bone-related proteinencoding gene.

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Autophagy in bone homeostasis and the onset of osteoporosis

Cited by 162 publications

References 223 publications

The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function

The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function

Sordaria macrospora: 25 years as a model organism for studying the molecular mechanisms of fruiting body development

Prioritization of osteoporosis-associated GWAS SNPs using epigenomics and transcriptomics

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