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Dive into the research topics where Chen-Xi Zheng is active.

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Featured researches published by Chen-Xi Zheng.


Scientific Reports | 2016

Mesenchymal progenitors in osteopenias of diverse pathologies: differential characteristics in the common shift from osteoblastogenesis to adipogenesis.

Bing-Dong Sui; Cheng-Hu Hu; Li Liao; Yichen Chen; Xinyi Zhang; Xin Fu; Chen-Xi Zheng; Meng Li; Ling Wu; Xinyi Zhao; Yan Jin

Osteoporosis is caused by pathologic factors such as aging, hormone deficiency or excess, inflammation, and systemic diseases like diabetes. Bone marrow stromal cells (BMSCs), the mesenchymal progenitors for both osteoblasts and adipocytes, are modulated by niche signals. In differential pathologic states, the pathological characteristics of BMSCs to osteoporoses and functional differences are unknown. Here, we detected that trabecular bone loss co-existed with increased marrow adiposity in 6 osteoporotic models, respectively induced by natural aging, accelerated senescence (SAMP6), ovariectomy (OVX), type 1 diabetes (T1D), excessive glucocorticoids (GIOP) and orchidectomy (ORX). Of the ex vivo characteristics of BMSCs, the colony-forming efficiency and the proliferation rate in aging, SAMP6, OVX, GIOP and ORX models decreased. The apoptosis and cellular senescence increased except in T1D, with up-regulation of p53 and p16 expression. The osteogenesis declined except in GIOP, with corresponding down-regulation of Runt-related transcription factor 2 (RUNX2) expression. The adipogenesis increased in 6 osteoporotic models, with corresponding up-regulation of Peroxisome proliferator activated receptor gamma (PPARγ) expression. These findings revealed differential characteristics of BMSCs in a common shift from osteoblastogenesis to adipogenesis among different osteoporoses and between sexes, and provide theoretical basis for the functional modulation of resident BMSCs in the regenerative therapy for osteoporosis.


Journal of Dental Research | 2016

Microenvironmental Views on Mesenchymal Stem Cell Differentiation in Aging

Bing-Dong Sui; Chenghu Hu; Chen-Xi Zheng; Yan Jin

Aging is characterized by common environmental changes, such as hormonal, immunologic, and metabolic disorders. These pathologic factors impair the capability of mesenchymal stem cells (MSCs) to generate and maintain functionalized tissue components, contributing to age-related tissue degeneration (e.g., osteoporosis). However, in organismal aging, whether the microenvironmental signals induce common or differential MSC compromise and how they interact at the molecular level in mediating the functional decline of MSCs are not fully understood. In this review, we discuss the respective contribution of microenvironmental pathologic factors to age-related MSC dysfunction—particularly, the shifted differentiation from osteoblasts to adipocytes of bone marrow–derived MSCs. The authors summarize recent works regarding mechanisms underlying MSC-biased differentiation under altered microenvironments, which involve the activation of key signaling pathways, intracellular oxidative stress, and posttranscriptional regulations. In addition, we compare the differential influences of systemic and local microenvironments on MSC differentiation based on our findings. The authors also propose strategies to rescue differentiation disorders of MSCs in aging via modulating microenvironments, by using signaling modulators, anti-inflammatory agents, antioxidants, and metabolic regulators and by promoting mobilization of systemic MSCs to local injury sites. The authors hope that these insights contribute to MSC-based organismal aging research and treatments.


Journal of Dental Research | 2016

microRNA-21 Contributes to Orthodontic Tooth Movement

N. Chen; Bing-Dong Sui; Chenghu Hu; J. Cao; Chen-Xi Zheng; R. Hou; Z.K. Yang; P. Zhao; Q. Chen; Q.J. Yang; Yan Jin; F. Jin

microRNAs could be mechanosensitive and emerge as critical posttranscriptional regulators in the bone-remodeling process. During orthodontic tooth movement (OTM), the application of mechanical force induces alveolar bone remodeling, but whether microRNAs respond to orthodontic force and contribute to OTM is unknown. microRNA-21 (miR-21) has been previously reported in vitro to mediate stretch-induced osteogenic differentiation of periodontal ligament stem cells and support osteoclast differentiation. In this study, the authors show that miR-21 responded to orthodontic force in periodontal tissue in a dose- and time-dependent manner and regulated the osteogenesis of human periodontal ligament stem cells following OTM. Using mmu-miR-21-deficient (miR-21-/-) mice, the authors discovered that mmu-miR-21 deficiency inhibited OTM and prevented force-induced maxillary bone loss. The authors found that miR-21-/- mice showed a normal skeletal phenotype in development and a similar alveolar bone formation rate to wild-type mice postnatally. During OTM, mmu-miR-21 regulated force-induced alveolar osteoblastogenesis in the tensile side, while no effects were detected in the compressive side. However, miR-21-/- mice showed inhibited alveolar osteoclastogenesis when compared with wild-type mice. During OTM, mmu-miR-21 deficiency blocked alveolar bone resorption in both the compressive and tensile sides. To dissect the mechanism by which miR-21 regulates alveolar bone remodeling, the authors screened the reported functional targets of miR-21 and found that periodontal expression of programmed cell death 4 (Pdcd4) was inhibited following OTM. Furthermore, mmu-miR-21 deficiency removed the suppression of Pdcd4 at both the mRNA and protein levels in the periodontium, resulting in upregulation of the downstream effector C-fos. Further analysis of OTM under lipopolysaccharide-induced periodontal inflammation showed that mmu-miR-21 mediated lipopolysaccharide (LPS)-accelerated OTM and that mmu-miR-21 deficiency blocked lipopolysaccharide-induced maxillary bone loss. In summary, these findings reveal a previously unrecognized mechanism that a microRNA can modulate OTM and alveolar bone remodeling under both normal and inflammatory microenvironments in vivo.


Aging Cell | 2017

Anti‐aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application

Pan Zhao; Bing-Dong Sui; Nu Liu; Yajie Lv; Chen-Xi Zheng; Yong-Bo Lu; Wen-Tao Huang; Cui-Hong Zhou; Ji Chen; Dan-Lin Pang; Dong-Dong Fei; Kun Xuan; Cheng-Hu Hu; Yan Jin

Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate‐activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age‐related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti‐aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR‐based anti‐aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects.


Scientific Reports | 2017

miR-21 deficiency inhibits osteoclast function and prevents bone loss in mice

Cheng-Hu Hu; Bing-Dong Sui; Fangying Du; Yi Shuai; Chen-Xi Zheng; Pan Zhao; Xiaorui Yu; Yan Jin

MicroRNAs emerge as critical post-transcriptional regulators in bone metabolism. We have previously reported in vitro that miR-21 promotes osteogenesis, while studies have also revealed miR-21 as a regulator of osteoclastogenesis and a promoter of osteoclast differentiation in vitro. However, in vivo data are still lacking in identifying skeletal function of miR-21, particularly its effects on osteoporosis. Here, using miR-21 knockout (miR-21−/−) mice, we investigated effects of miR-21 on bone development, bone remodeling and bone loss. Unexpectedly, miR-21−/− mice demonstrated normal skeletal phenotype in development and maintained osteoblastogenesis in vivo. Besides, miR-21−/− mice showed increased receptor activator of nuclear factor κB ligand (RANKL) and decreased osteoprotegerin (OPG) through miR-21 targeting Sprouty 1 (Spry1). Nevertheless, interestingly, miR-21 deficiency promoted trabecular bone mass accrual physiologically. Furthermore, in pathological states, the protection of bone mass was prominent in miR-21−/− mice. These skeletal effects were attributed to inhibition of bone resorption and osteoclast function by miR-21 deficiency through miR-21 targeting programmed cell death 4 (PDCD4), despite the existence of RANKL. As far as we know, this is the first in vivo evidence of a pro-osteoclastic microRNA. Together, these findings clarified function of miR-21 in bone metabolism, particularly uncovering osteo-protective potential of miR-21 inactivation in osteoporosis.


Theranostics | 2017

Recipient Glycemic Micro-environments Govern Therapeutic Effects of Mesenchymal Stem Cell Infusion on Osteopenia.

Bing-Dong Sui; Cheng-Hu Hu; Chen-Xi Zheng; Yi Shuai; Xiaoning He; Ping-Ping Gao; Pan Zhao; Meng Li; Xinyi Zhang; Tao He; Kun Xuan; Yan Jin

Therapeutic effects of mesenchymal stem cell (MSC) infusion have been revealed in various human disorders, but impacts of diseased micro-environments are only beginning to be noticed. Donor diabetic hyperglycemia is reported to impair therapeutic efficacy of stem cells. However, whether recipient diabetic condition also affects MSC-mediated therapy is unknown. We and others have previously shown that MSC infusion could cure osteopenia, particularly in ovariectomized (OVX) mice. Here, we discovered impaired MSC therapeutic effects on osteopenia in recipient type 1 diabetes (T1D). Through intensive glycemic control by daily insulin treatments, therapeutic effects of MSCs on osteopenia were maintained. Interestingly, by only transiently restoration of recipient euglycemia using single insulin injection, MSC infusion could also rescue T1D-induced osteopenia. Conversely, under recipient hyperglycemia induced by glucose injection in OVX mice, MSC-mediated therapeutic effects on osteopenia were diminished. Mechanistically, recipient hyperglycemic micro-environments reduce anti-inflammatory capacity of MSCs in osteoporotic therapy through suppressing MSC interaction with T cells via the Adenosine monophosphate-activated protein kinase (AMPK) pathway. We further revealed in diabetic micro-environments, double infusion of MSCs ameliorated osteopenia by anti-inflammation, attributed to the first transplanted MSCs which normalized the recipient glucose homeostasis. Collectively, our findings uncover a previously unrecognized role of recipient glycemic conditions controlling MSC-mediated therapy, and unravel that fulfillment of potent therapeutic effects of MSCs requires tight control of recipient micro-environments.


Biomaterials | 2017

Stem cell-based bone regeneration in diseased microenvironments: Challenges and solutions

Bing-Dong Sui; Cheng-Hu Hu; An-Qi Liu; Chen-Xi Zheng; Kun Xuan; Yan Jin

Restoration of extensive bone loss and defects remain as an unfulfilled challenge in modern medicine. Given the critical contributions to bone homeostasis and diseases, mesenchymal stem cells (MSCs) have shown great promise to jumpstart and facilitate bone healing, with immense regenerative potential in both pharmacology-based endogenous MSC rescue/mobilization in skeletal diseases and emerging application of MSC transplantation in bone tissue engineering and cytotherapy. However, efficacy of MSC-based bone regeneration was not always achieved; particularly, fulfillment of MSC-mediated bone healing in diseased microenvironments of host comorbidities remains as a major challenge. Indeed, impacts of diseased microenvironments on MSC function rely not only on the dynamic regulation of resident MSCs by surrounding niche to convoy pathological signals of bone, but also on the profound interplay between transplanted MSCs and recipient components that mediates and modulates therapeutic effects on skeletal conditions. Accordingly, novel solutions have recently been developed, including improving resistance of MSCs to diseased microenvironments, recreating beneficial microenvironments to guarantee MSC-based regeneration, and usage of subcellular vesicles of MSCs in cell-free therapies. In this review, we summarize state-of-the-art knowledge regarding applications and challenges of MSC-mediated bone healing, further offering principles and effective strategies to optimize MSC-based bone regeneration in aging and diseases.


Scientific Reports | 2018

Adipose mesenchymal stem cells from osteoporotic donors preserve functionality and modulate systemic inflammatory microenvironment in osteoporotic cytotherapy

Chen-Xi Zheng; Bing-Dong Sui; Nu Liu; Cheng-Hu Hu; Tao He; Xinyi Zhang; Pan Zhao; Ji Chen; Kun Xuan; Yan Jin

Maintenance of bone homeostasis against diseased microenvironments remains as a major challenge. Recently, mesenchymal stem cells (MSCs) have been unravelled as potent microenvironmental modulators, the systemic infusion of which in cytotherapy can prevent or rescue extensive bone loss via anti-inflammation. However, MSCs also accept microenvironmental regulations; particularly, MSCs from bone marrow (BMMSCs) are prone to pathological microenvironmental factors of bone. In this study, we discovered that BMMSCs from osteoporotic donors of ovariectomized (OVX) mice lost their anti-inflammatory capability and failed to prevent bone loss when infused back into OVX recipients. Nevertheless, MSCs from adipose tissues (ADMSCs) preserved their anti-inflammatory capacity, despite diseased microenvironments of OVX donors, and continued to show protective effects on bone in OVX recipients. In the cellular level, the anti-inflammatory superiority of osteoporotic donor-derived ADMSCs over BMMSCs existed in their distinctive capability to induce T-cell apoptosis, which was molecularly attributed to retained expression levels of critical immunomodulatory genes. Furthermore, these functional discrepancies of BMMSCs and ADMSCs were due to differential stemness, energy metabolism and anti-oxidative defence system, underlying general disparity in their cellular states. Collectively, our findings optimize osteoporotic cytotherapy by using ADMSCs in resistance to and in modulation of diseased microenvironments.


Journal of Tissue Engineering and Regenerative Medicine | 2018

Reconstruction of structure and function in tissue engineering of solid organs: Toward simulation of natural development based on decellularization

Chen-Xi Zheng; Bing-Dong Sui; Cheng-Hu Hu; Xinyu Qiu; Pan Zhao; Yan Jin

Failure of solid organs, such as the heart, liver, and kidney, remains a major cause of the worlds mortality due to critical shortage of donor organs. Tissue engineering, which uses elements including cells, scaffolds, and growth factors to fabricate functional organs in vitro, is a promising strategy to mitigate the scarcity of transplantable organs. Within recent years, different construction strategies that guide the combination of tissue engineering elements have been applied in solid organ tissue engineering and have achieved much progress. Most attractively, construction strategy based on whole‐organ decellularization has become a popular and promising approach, because the overall structure of extracellular matrix can be well preserved. However, despite the preservation of whole structure, the current constructs derived from decellularization‐based strategy still perform partial functions of solid organs, due to several challenges, including preservation of functional extracellular matrix structure, implementation of functional recellularization, formation of functional vascular network, and realization of long‐term functional integration. This review overviews the status quo of solid organ tissue engineering, including both advances and challenges. We have also put forward a few techniques with potential to solve the challenges, mainly focusing on decellularization‐based construction strategy. We propose that the primary concept for constructing tissue‐engineered solid organs is fabricating functional organs based on intact structure via simulating the natural development and regeneration processes.


Experimental and Molecular Medicine | 2018

Resveratrol enhances the functionality and improves the regeneration of mesenchymal stem cell aggregates

Yi-Jing Wang; Pan Zhao; Bing-Dong Sui; Nu Liu; Cheng-Hu Hu; Ji Chen; Chen-Xi Zheng; An-Qi Liu; Kun Xuan; Ya-Ping Pan; Yan Jin

Mesenchymal stem cell (MSC)-based regeneration, specifically cell aggregate or cell sheet engineering, is a promising approach for tissue reconstruction. Considering the advantages of ease of harvest and lack of immune rejection, the application of autologous MSCs (i.e., patients’ own MSCs) in regenerative medicine has developed considerable interest. However, the impaired cell viability and regenerative potential following MSCs impacted by disease remain a major challenge. Resveratrol (RSV) exhibits reliable and extensive rejuvenative activities that have received increasing clinical attention. Here, we uncovered that resveratrol enhances the functionality and improves the regeneration of mesenchymal stem cell aggregates. Periodontal ligament MSCs (PDLSCs) from normal control subjects (N-PDLSCs) and periodontitis patients (P-PDLSCs) were investigated. Compared to N-PDLSCs, P-PDLSCs were less capable of forming cell aggregates, and P-PDLSC aggregates showed impaired osteogenesis and regeneration. These functional declines could be mimicked in N-PDLSCs by tumor necrosis factor alpha (TNF-α) treatment. Notably, a TNF-α-induced functional decline in N-PDLSC aggregates was rescued by RSV application. More importantly, in both N-PDLSCs and P-PDLSCs, RSV promoted cell aggregate formation and improved their osteogenic potential. Furthermore, as proven ectopically in vivo, the tissue regenerative capability of P-PDLSC aggregates was also enhanced after RSV treatment during aggregate formation in vitro. Finally, in a rat in situ regeneration model, we successfully applied both N-PDLSC aggregates and P-PDLSC aggregates to repair periodontal defects upon long-term functional improvements by RSV preconditioning. Together, our data unravel a novel methodology for using pharmacology (i.e., RSV)-based cell aggregate engineering to improve the functionality and facilitate the regeneration of MSCs from both healthy and inflammatory microenvironments, shedding light on improving the application of autologous MSC-mediated regenerative medicine.Regenerative medicine: Red wine compound helps rejuvenate stem cellsA molecule found in the skin of red grapes enhances the regenerative capacity of adult stem cells. Researchers in China led by Yan Jin from Fourth Military Medical University, Xi’an, and Ya-Ping Pan from China Medical University, Shenyang, isolated stem cells capable of making the different specialized cells found in the skeletal tissues from the connective tissue located at the root of tooth-bearing bones. They showed that stem cells taken from people with serious gum disease could not mature and develop into tissue-forming aggregates as well as stem cells taken from healthy individuals. Treatment of healthy stem cells with a pro-inflammatory signaling molecule impaired development, but subsequent exposure to resveratrol, the compound in grape skin, restored cellular health. Resveratrol also promoted regeneration in the diseased stem cells and in rodent models of gum disease.

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Bing-Dong Sui

Fourth Military Medical University

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Yan Jin

Fourth Military Medical University

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Cheng-Hu Hu

Fourth Military Medical University

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Pan Zhao

Fourth Military Medical University

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Kun Xuan

Fourth Military Medical University

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Ji Chen

Fourth Military Medical University

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Nu Liu

Fourth Military Medical University

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Xinyi Zhang

Fourth Military Medical University

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An-Qi Liu

Fourth Military Medical University

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Chenghu Hu

Fourth Military Medical University

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