The versatile hippo pathway in oral-maxillofacial development and bone remodeling

Xiang, Lin; Yu, Hui; Wang, Bin; Yuan, Ying; Zhang, Qin; Rui, Yong; Gong, Ping; Wu, Yingying

doi:10.1016/j.ydbio.2018.05.017

Cited by 14 publications

(7 citation statements)

References 95 publications

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“…Downstream YAP/TAZ regulation is in fact tightly involved in mechanosensing and mechanotransduction both in bone and muscle as well as in many other cells, especially endothelial cells (see Section 3.3). Recently, the Ras-related GTPase RAP2 was identified to mediate mechanoresponse in this context, and it is also involved in stiffness response [55,115,116].…”

Section: Principles Of Bone Formation Maintenance and Regenerationmentioning

confidence: 99%

Interactions between Muscle and Bone—Where Physics Meets Biology

et al. 2020

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Muscle and bone interact via physical forces and secreted osteokines and myokines. Physical forces are generated through gravity, locomotion, exercise, and external devices. Cells sense mechanical strain via adhesion molecules and translate it into biochemical responses, modulating the basic mechanisms of cellular biology such as lineage commitment, tissue formation, and maturation. This may result in the initiation of bone formation, muscle hypertrophy, and the enhanced production of extracellular matrix constituents, adhesion molecules, and cytoskeletal elements. Bone and muscle mass, resistance to strain, and the stiffness of matrix, cells, and tissues are enhanced, influencing fracture resistance and muscle power. This propagates a dynamic and continuous reciprocity of physicochemical interaction. Secreted growth and differentiation factors are important effectors of mutual interaction. The acute effects of exercise induce the secretion of exosomes with cargo molecules that are capable of mediating the endocrine effects between muscle, bone, and the organism. Long-term changes induce adaptations of the respective tissue secretome that maintain adequate homeostatic conditions. Lessons from unloading, microgravity, and disuse teach us that gratuitous tissue is removed or reorganized while immobility and inflammation trigger muscle and bone marrow fatty infiltration and propagate degenerative diseases such as sarcopenia and osteoporosis. Ongoing research will certainly find new therapeutic targets for prevention and treatment.

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Section: Principles Of Bone Formation Maintenance and Regenerationmentioning

confidence: 99%

Interactions between Muscle and Bone—Where Physics Meets Biology

et al. 2020

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“…Although animal GCKs have been extensively investigated, their evolutionary history remains unclear ( Sebé-Pedrós et al 2012 , 2016 ). Molecular mechanisms, underlying multiple GCK-related disease phenotypes in mammals, also require further investigation ( Maugeri-Saccà and De Maria 2018 ; Xiang et al 2018 ). Moreover, new GCK targets, regulators, and interaction partners are being steadily identified ( Johnson and Halder 2014 ; Meng et al 2016 ).…”

mentioning

confidence: 99%

A Hippo Pathway-Related GCK Controls Both Sexual and Vegetative Developmental Processes in the Fungus Sordaria macrospora

et al. 2018

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The supramolecular striatin-interacting phosphatases and kinases (STRIPAK) complex is conserved from yeast to human, and regulates a variety of key biological processes. In animals, this complex consists of the scaffold protein striatin, the protein phosphatase 2A, and kinases, such as germinal center kinase (GCK) III and GCKIV family members, as well as other associated proteins. The STRIPAK complex was identified as a negative regulator of the Hippo pathway, a large eukaryotic signaling network with a core composed of a GCK and a nuclear Dbf2-related kinase. The signaling architecture of the Hippo core resembles the fungal septation initiation network (SIN) that regulates cytokinesis in fission yeast as well as septation in filamentous fungi. In the filamentous model fungus Sordaria macrospora, core components of the STRIPAK complex have been functionally described and the striatin homolog PRO11 has been shown to interact with the GCK SmKIN3. However, the exact role of SmKIN3 in fungal development has not yet been fully elucidated. Here, we provide comprehensive genetic and functional analysis of SmKIN3 from S. macrospora. Using deletion mutants and site-directed mutagenesis, along with phenotypic and phylogenetic analysis, we provide compelling evidence that SmKIN3 is involved in fruiting body formation, hyphal fusion, and septation. Strains carrying the ATP-binding mutant SmKIN3K39R, as well as a double-deletion strain lacking SmKIN3 and the core STRIPAK subunit PRO11, also revealed severe developmental defects. Collectively, this study suggests that SmKIN3 links both the SIN and STRIPAK complex, thereby regulating multiple key cellular processes.

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“…It is unclear how several of the identified pathways targeted specifically by femoral bone miRNAs are associated with BMD, with the exception of the Hippo signaling pathway. The Hippo signaling pathway is important for stem cell function, bone development, and bone remodeling via interactions with, eg, the transforming growth factor beta (TGF‐β)/SMAD pathway, Wnt signaling, and the transcription factor RUNX2 (RUNX family transcription factor 2) . Supporting the relevance of these findings in bone tissue, 22 of 46 ncRNAs have been shown to be important for bone cell differentiation and function in cell and animal models (Table S5).…”

Section: Discussionmentioning

confidence: 91%

Distinct Subsets of Noncoding RNAs Are Strongly Associated With BMD and Fracture, Studied in Weight-Bearing and Non–Weight-Bearing Human Bone

Gautvik

Günther

Prijatelj

et al. 2020

Journal of Bone and Mineral Research

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We investigated mechanisms resulting in low bone mineral density (BMD) and susceptibility to fracture by comparing noncoding RNAs (ncRNAs) in biopsies of non–weight‐bearing (NWB) iliac (n = 84) and weight bearing (WB) femoral (n = 18) postmenopausal bone across BMDs varying from normal (T‐score > −1.0) to osteoporotic (T‐score ≤ −2.5). Global bone ncRNA concentrations were determined by PCR and microchip analyses. Association with BMD or fracture, adjusted by age and body mass index, were calculated using linear and logistic regression and least absolute shrinkage and selection operator (Lasso) analysis. At 10% false discovery rate (FDR), 75 iliac bone ncRNAs and 94 femoral bone ncRNAs were associated with total hip BMD. Eight of the ncRNAs were common for the two sites, but five of them (miR‐484, miR‐328‐3p, miR‐27a‐5p, miR‐28‐3p, and miR‐409‐3p) correlated positively to BMD in femoral bone, but negatively in iliac bone. Of predicted pathways recognized in bone metabolism, ECM‐receptor interaction and proteoglycans in cancer emerged at both sites, whereas fatty acid metabolism and focal adhesion were only identified in iliac bone. Lasso analysis and cross‐validations identified sets of nine bone ncRNAs correlating strongly with adjusted total hip BMD in both femoral and iliac bone. Twenty‐eight iliac ncRNAs were associated with risk of fracture (FDR < 0.1). The small nucleolar RNAs, RNU44 and RNU48, have a function in stabilization of ribosomal RNAs (rRNAs), and their association with fracture and BMD suggest that aberrant processing of rRNAs may be involved in development of osteoporosis. Cis‐eQTL (expressed quantitative trait loci) analysis of the iliac bone biopsies identified two loci associated with microRNAs (miRNAs), one previously identified in a heel‐BMD genomewide association study (GWAS). In this comprehensive investigation of the skeletal genetic background in postmenopausal women, we identified functional bone ncRNAs associated to fracture and BMD, representing distinct subsets in WB and NWB skeletal sites. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

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The versatile hippo pathway in oral-maxillofacial development and bone remodeling

Cited by 14 publications

References 95 publications

Interactions between Muscle and Bone—Where Physics Meets Biology

Interactions between Muscle and Bone—Where Physics Meets Biology

A Hippo Pathway-Related GCK Controls Both Sexual and Vegetative Developmental Processes in the Fungus Sordaria macrospora

Distinct Subsets of Noncoding RNAs Are Strongly Associated With BMD and Fracture, Studied in Weight-Bearing and Non–Weight-Bearing Human Bone

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