Osteoblastic lysosome plays a central role in mineralization

Iwayama, Tomoaki; Okada, Tomoko; Ueda, Tomiko; Tomita, Kiwako; Matsumoto, Shigeto; Takedachi, Masahide; Wakisaka, Satoshi; Noda, Tetsuji; Ogura, Taku; Okano, Tamon; Fratzl, Peter; Ogura, Toshihiko; Murakami, Shinya

doi:10.1126/sciadv.aax0672

Cited by 77 publications

(59 citation statements)

References 47 publications

(66 reference statements)

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“…Instead, the mitochondria became electron‐dense masses and eventually developed into large‐sized biomineral precursors, undergoing a transportation process of mitophagy (Figure G). It appeared that smaller‐sized precursors were produced first, which was consistent with a previous study . Despite the time sequence, all biomineral precursors originated from mitochondria.…”

Section: Resultssupporting

confidence: 89%

“…Boonrungsiman et al5a observe direct transportation of calcium ions and possibly phosphate ions between mitochondria and intracellular vesicles. Another two studies5b,6 demonstrate that ACP precursors are transferred from mitochondria via the lysosomal pathway. Until now, observations on the continuous in vivo process of biomineralization are lacking, and there is still no evidence revealing the mechanisms of formation of the mitochondrial granules.…”

Section: Introductionmentioning

confidence: 99%

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Biomineral Precursor Formation Is Initiated by Transporting Calcium and Phosphorus Clusters from the Endoplasmic Reticulum to Mitochondria

Tang

Wei

et al. 2020

Advanced Science

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Mineral granules in the mitochondria of bone‐forming cells are thought to be the origin of biomineral precursors, which are transported to extracellular matrices to initiate cell‐mediated biomineralization. However, no evidence has revealed how mitochondrial granules form. This study indicates that mitochondrial granules are initiated by transporting calcium and phosphorus clusters from the endoplasmic reticulum (ER) to mitochondria based on detailed observations of the continuous process of mouse parietal bone development as well as in vitro biomineralization in bone‐forming cells. Nanosized biomineral precursors (≈30 nm in diameter), which originate from mitochondrial granules, initiate intrafibrillar mineralization of collagen as early as embryonic day 14.5. Both in vivo and in vitro studies further reveal that formation of mitochondrial granules is induced by the ER. Elevated levels of intracellular calcium or phosphate ions, which can be induced by treatment with ionomycin and black phosphorus, respectively, accelerate formation of the calcium and phosphorus clusters on ER membranes and ultimately promote biomineralization. These findings provide a novel insight into biomineralization and bone formation.

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Section: Resultssupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Biomineral Precursor Formation Is Initiated by Transporting Calcium and Phosphorus Clusters from the Endoplasmic Reticulum to Mitochondria

Tang

Wei

et al. 2020

Advanced Science

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“…After 9 h, the PM2.5 aggregates were covered with the region of low density, which we assumed to be intracellular membrane-like structures (Fig. 2b, 9 h panels) on the basis of our previous study 24,28 . After 24 h of culture with PM2.5, the number of particulates and aggregates decreased in the whole visual field ( Fig.…”

Section: Resultsmentioning

confidence: 95%

“…When an electron beam (EB) was applied to the W-coated SiN film, the EB was scattered and mostly absorbed by the tungsten layer, so that biological samples were protected from damages by the EB 21 . Our SE-ADM system has been successfully used for high-contrast nano-level imaging of biological specimens such as cultured mouse cancer cells (4T1E/M3) 22 , 23 and mouse osteoblastic cells (KUSA-A1) 24 .…”

Section: Introductionmentioning

confidence: 99%

Nanoscale observation of PM2.5 incorporated into mammalian cells using scanning electron-assisted dielectric microscope

Okada

Iwayama

Murakami

et al. 2021

Sci Rep

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PM2.5 has been correlated with risk factors for various diseases and infections. It promotes tissue injury by direct effects of particle components. However, effects of PM2.5 on cells have not been fully investigated. Recently, we developed a novel imaging technology, scanning electron-assisted dielectric-impedance microscopy (SE-ADM), which enables observation of various biological specimens in aqueous solution. In this study, we successfully observed PM2.5 incorporated into living mammalian cells in culture media. Our system directly revealed the process of PM2.5 aggregation in the cells at a nanometre resolution. Further, we found that the PM2.5 aggregates in the intact cells were surrounded by intracellular membrane-like structures of low-density in the SE-ADM images. Moreover, the PM2.5 aggregates were shown by confocal Raman microscopy to be located inside the cells rather than on the cell surface. We expect our method to be applicable to the observation of various nanoparticles inside cells in culture media.

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“…The declined transportation capacity of the endoplasmic reticulum also decreases the transfer and distribution of mitochondria, suppressing intracellular homeostasis in senescent osteocytes [ 21 ]. Lysosomes are required to transport mineral-containing matrix vesicles out of osteoblastic cells [ 22 ], whereas the lack of lysosomal enzymes results in lysosome storage-mediated skeletal disorders [ 23 ]. Clearance of dysfunctional organelles is required to maintain biological activity of osteoblasts, osteoclasts, and skeletal health.…”

Section: Organelle Machinery Regulating Osteoblastic Activitymentioning

confidence: 99%

Epigenetic Regulation of Skeletal Tissue Integrity and Osteoporosis Development

Chen

Lian

Kuo

et al. 2020

IJMS

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Bone turnover is sophisticatedly balanced by a dynamic coupling of bone formation and resorption at various rates. The orchestration of this continuous remodeling of the skeleton further affects other skeletal tissues through organ crosstalk. Chronic excessive bone resorption compromises bone mass and its porous microstructure as well as proper biomechanics. This accelerates the development of osteoporotic disorders, a leading cause of skeletal degeneration-associated disability and premature death. Bone-forming cells play important roles in maintaining bone deposit and osteoclastic resorption. A poor organelle machinery, such as mitochondrial dysfunction, endoplasmic reticulum stress, and defective autophagy, etc., dysregulates growth factor secretion, mineralization matrix production, or osteoclast-regulatory capacity in osteoblastic cells. A plethora of epigenetic pathways regulate bone formation, skeletal integrity, and the development of osteoporosis. MicroRNAs inhibit protein translation by binding the 3′-untranslated region of mRNAs or promote translation through post-transcriptional pathways. DNA methylation and post-translational modification of histones alter the chromatin structure, hindering histone enrichment in promoter regions. MicroRNA-processing enzymes and DNA as well as histone modification enzymes catalyze these modifying reactions. Gain and loss of these epigenetic modifiers in bone-forming cells affect their epigenetic landscapes, influencing bone homeostasis, microarchitectural integrity, and osteoporotic changes. This article conveys productive insights into biological roles of DNA methylation, microRNA, and histone modification and highlights their interactions during skeletal development and bone loss under physiological and pathological conditions.

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Osteoblastic lysosome plays a central role in mineralization

Cited by 77 publications

References 47 publications

Biomineral Precursor Formation Is Initiated by Transporting Calcium and Phosphorus Clusters from the Endoplasmic Reticulum to Mitochondria

Biomineral Precursor Formation Is Initiated by Transporting Calcium and Phosphorus Clusters from the Endoplasmic Reticulum to Mitochondria

Nanoscale observation of PM2.5 incorporated into mammalian cells using scanning electron-assisted dielectric microscope

Epigenetic Regulation of Skeletal Tissue Integrity and Osteoporosis Development

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