Contribution of Mitophagy to Cell‐Mediated Mineralization: Revisiting a 50‐Year‐Old Conundrum

Pei, Dan; Sun, Jin; Zhu, Chun hui; Tian, Fucong; Jiao, Kai; Anderson, Matthew; Yiu, Cky; Huang, Cui; Jin, Chang xiong; Bergeron, Brian E.; Chen, Ji Hua; Tay, Franklin R.; Niu, Li Na

doi:10.1002/advs.201800873

Cited by 71 publications

(55 citation statements)

References 66 publications

(91 reference statements)

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“…Also, the process of mitophagy was proven to participate in the cell-mediated biomineralization process. To be specific, the amorphous calcium phosphate, which was the precursor in biomineralization, could trigger mitophagy to transport intracellularly via the autophagosome and released to the extracellular matrix via exocytosis ( Pei et al, 2018 ). In this study, with the relative expression of mitophagy-related gene upregulated at 5 days, the osteogenesis-related gene expression of SLM-CO group was promoted, which was consistent with other relevant studies ( Hyzy et al, 2016 ; H. Wang et al, 2018 ; Yu et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Enhanced Osseointegration by the Hierarchical Micro-Nano Topography on Selective Laser Melting Ti-6Al-4V Dental Implants

Shu

Zhang

Sun

et al. 2021

Front. Bioeng. Biotechnol.

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Currently, selective laser melting (SLM) has been thriving in implant dentistry for on-demand fabricating dental implants. Based on the coarse microtopography of SLM titanium surfaces, constructing nanostructure to form the hierarchical micro-nano topography is effective in enhancing osseointegration. Given that current nanomodification techniques of SLM implants, such as anodization and hydrothermal treatment, are facing the inadequacy in costly specific apparatus and reagents, there has been no recognized nanomodified SLM dental implants. The present study aimed to construct hierarchical micro-nano topography on self-made SLM dental implants by a simple and safe inorganic chemical oxidation, and to evaluate its contribution on osteoblastic cells bioactivity and osseointegration. The surface chemical and physical parameters were characterized by FE-SEM, EDS, profilometer, AFM, and contact angle meter. The alteration on bioactivity of MG-63 human osteoblastic cells were detected by qRT-PCR. Then the osseointegration was assessed by implanting implants on the femur condyle of New Zealand Rabbits. The hierarchical micro-nano topography was constituted by the microrough surface of SLM implants and nanoneedles (diameter: 20∼50 nm, height: 150∼250 nm), after nanomodifying SLM implants in 30% hydrogen peroxide and 30% hydrochloride acid (volume ratio 1:2.5) at room temperature for 36 h. Low chemical impurities content and high hydrophilicity were observed in the nanomodified group. Cell experiments on the nanomodified group showed higher expression of mitophagy related gene (PINK1, PARKIN, LC3B, and LAMP1) at 5 days and higher expression of osteogenesis related gene (Runx2 and OCN) at 14 days. In the early stage of bone formation, the nanomodified SLM implants demonstrated higher bone-to-implant contact. Intriguingly, the initial bone-to-implant contact of nanomodified SLM implants consisted of more mineralized bone with less immature osteoid. After the cessation of bone formation, the bone-to-implant contact of nanomodified SLM implants was equal to untreated SLM implants and marketable TixOs implants. The overall findings indicated that the inorganic chemical oxidized hierarchical micro-nano topography could enhance the bioactivity of osteoblastic cells, and consequently promote the peri-implant bone formation and mineralization of SLM dental implants. This study sheds some light on improvements in additive manufactured dental implants.

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Section: Discussionmentioning

confidence: 99%

Enhanced Osseointegration by the Hierarchical Micro-Nano Topography on Selective Laser Melting Ti-6Al-4V Dental Implants

Shu

Zhang

Sun

et al. 2021

Front. Bioeng. Biotechnol.

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“…markedly impedes osteoblast survival. Recent studies have suggested that mitophagy is important in regulating osteoblast survival and function (Pei et al, 2018a;Zhao et al, 2020). Nevertheless, the involvement of osteoblast mitophagy in the pathogenesis of GIOP is not clear.…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that GC excess interrupts mitochondrial function and prolonged exposure deteriorates mitochondrial integrity leading to release of pro-apoptotic proteins, reactive oxygen species (ROS) accumulation, and ineffective generation of ATP that markedly impedes osteoblast survival. Recent studies have suggested that mitophagy is important in regulating osteoblast survival and function ( Pei et al., 2018a ; Zhao et al., 2020 ). Nevertheless, the involvement of osteoblast mitophagy in the pathogenesis of GIOP is not clear.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, GC usage have been reported to inhibit osteoblast autophagy and this effect plays a pivotal role in the pathogenesis of GIOP (Han et al, 2018;Lian et al, 2018;Gremminger et al, 2019;Wang et al, 2019). Recently a specialized form of autophagy that specifically degrades dysfunctional or redundant mitochondria, termed mitophagy, was found to contribute to the mineralization function of osteoblasts (Pei et al, 2018a). Under homeostatic conditions, PTEN induced putative kinase 1 (PINK1) translocates to the inner membrane of the mitochondria where it is rapidly degraded.…”

Section: Introductionmentioning

confidence: 99%

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Vitamin K2 Can Rescue the Dexamethasone-Induced Downregulation of Osteoblast Autophagy and Mitophagy Thereby Restoring Osteoblast Function In Vitro and In Vivo

et al. 2020

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Chronic long-term glucocorticoids (GC) use is associated with glucocorticoid-induced osteoporosis (GIOP) by inhibiting the survival and impairing the functions of osteoblasts. Autophagy and mitophagy play key roles in osteoblast differentiation, mineralization and survival, and mounting evidence have implicated osteoblast autophagy and mitophagy as a novel mechanism in the pathogenesis of GIOP. Vitamin K2 (VK2) is an essential nutrient supplement that have been shown to exert protective effects against osteoporotic bone loss including GIOP. In this study, we showed that the glucocorticoid dexamethasone (Dex) deregulated osteoblast autophagy and mitophagy by downregulating the expression of autophagic and mitophagic markers LC3-II, PINK1, Parkin. This consequently led to inhibition of osteoblast differentiation and mineralization function in vitro. Interestingly, co-treatment with VK2 significantly attenuated the Dex-induced downregulation of LC3-II, PINK1, Parkin, thereby restoring autophagic and mitophagic processes and normal osteoblastic activity. In addition, using an established rat model of GIOP, we showed that VK2 administration can protect rats against the deleterious effects of Dex on bone by reinstating autophagic and mitophagic activities in bone tissues. Collectively, our results provide new insights into the role of osteoblast autophagy and mitophagy in GIOP. Additionally, the use of VK2 supplementation to augment osteoblast autophagy/mitophagy may significantly improve clinical outcomes of GIOP patients.

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“…Conversely, knock down of PINK1 in human dental pulp stem cells (hDPSCs) results in impaired osteogenesis (Pei et al, 2018 ). Possibly, mitophagy is underpinning dual roles within VSMCs by (i) contributing to bone formation via exocytosis of Ca and Pi-filled mitochondrial-derived vesicles packed in autolysosomes to the extracellular matrix and (ii) clearing dysfunctional mitochondria within calcified VSMCs.…”

Section: Mitochondrial Quality Control In Vascular Calcificationmentioning

confidence: 99%

Mitochondrial Dysfunction: Cause or Consequence of Vascular Calcification?

Phadwal

Vrahnas

Ganley

et al. 2021

Front. Cell Dev. Biol.

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Mitochondria are crucial bioenergetics powerhouses and biosynthetic hubs within cells, which can generate and sequester toxic reactive oxygen species (ROS) in response to oxidative stress. Oxidative stress-stimulated ROS production results in ATP depletion and the opening of mitochondrial permeability transition pores, leading to mitochondria dysfunction and cellular apoptosis. Mitochondrial loss of function is also a key driver in the acquisition of a senescence-associated secretory phenotype that drives senescent cells into a pro-inflammatory state. Maintaining mitochondrial homeostasis is crucial for retaining the contractile phenotype of the vascular smooth muscle cells (VSMCs), the most prominent cells of the vasculature. Loss of this contractile phenotype is associated with the loss of mitochondrial function and a metabolic shift to glycolysis. Emerging evidence suggests that mitochondrial dysfunction may play a direct role in vascular calcification and the underlying pathologies including (1) impairment of mitochondrial function by mineral dysregulation i.e., calcium and phosphate overload in patients with end-stage renal disease and (2) presence of increased ROS in patients with calcific aortic valve disease, atherosclerosis, type-II diabetes and chronic kidney disease. In this review, we discuss the cause and consequence of mitochondrial dysfunction in vascular calcification and underlying pathologies; the role of autophagy and mitophagy pathways in preventing mitochondrial dysfunction during vascular calcification and finally we discuss mitochondrial ROS, DRP1, and HIF-1 as potential novel markers and therapeutic targets for maintaining mitochondrial homeostasis in vascular calcification.

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Contribution of Mitophagy to Cell‐Mediated Mineralization: Revisiting a 50‐Year‐Old Conundrum

Cited by 71 publications

References 66 publications

Enhanced Osseointegration by the Hierarchical Micro-Nano Topography on Selective Laser Melting Ti-6Al-4V Dental Implants

Enhanced Osseointegration by the Hierarchical Micro-Nano Topography on Selective Laser Melting Ti-6Al-4V Dental Implants

Vitamin K2 Can Rescue the Dexamethasone-Induced Downregulation of Osteoblast Autophagy and Mitophagy Thereby Restoring Osteoblast Function In Vitro and In Vivo

Mitochondrial Dysfunction: Cause or Consequence of Vascular Calcification?

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