Micro<scp>RNA</scp>‐31a‐5p from aging <scp>BMSC</scp>s links bone formation and resorption in the aged bone marrow microenvironment

Xu, Rongyao; Shen, Xiang; Si, Yameng; Fu, Yu; Zhu, Weiwen; Xiao, Tao; Fu, Zongyun; Zhang, Ping; Cheng, Jie; Jiang, Hongbing

doi:10.1111/acel.12794

Cited by 177 publications

(153 citation statements)

References 62 publications

(75 reference statements)

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“…Western blot was performed using methods previously described in refs. 26 and 27. Briefly, cell lysates were separated on polyacrylamide–sodium dodecyl sulfate gel and electroblotted onto nitrocellulose membranes (Bio‐Rad, Hercules, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Zoledronic acid promotes TLR‐4‐mediated M1 macrophage polarization in bisphosphonate‐related osteonecrosis of the jaw

Zhu

et al. 2019

FASEB j.

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Bisphosphonate‐related osteonecrosis of the jaw (BRONJ) is a detrimental side effect of the long‐term administration of bisphosphonates. Although macrophages were reported to be an important mediator of BRONJ, the detailed potential mechanism of BRONJ remains unclear. Here, we reported an elevated TLR‐4 expression in macrophages under action of zoledronic acid (ZA), resulting in enhanced M1 macrophage polarization and decreased M2 macrophage polarization both in vitro and in vivo. After inhibiting the TLR‐4 signaling pathway, the activation of the TLR‐4/NF‐κB signaling pathway and the induction of NF‐κB nuclear translocation and production of proinflammatory cytokines by ZA were suppressed in macrophages, thereby inhibiting M1 macrophage polarization. By utilizing the TLR‐4−/− mice, development of BRONJ was markedly ameliorated, and M1 macrophages were significantly attenuated in the extraction socket tissues in the TLR‐4−/− mice. Importantly, the systemic administration of the TLR‐4 inhibitor TAK‐242 improved the wound healing of the extraction socket and decreased the incidence rate of BRONJ. Taken together, our findings suggest that TLR‐4‐mediated macrophage polarization participates in the pathogenesis of BRONJ in mice, and TLR‐4 may be a potential target for the prevention and therapeutic treatment of BRONJ.—Zhu, W., Xu, R., Du, J., Fu, Y., Li, S., Zhang, P., Liu, L., Jiang, H. Zoledronic acid promotes TLR‐4‐mediated M1 macrophage polarization in bisphosphonate‐related osteonecrosis of the jaw. FASEB J. 33, 5208–5219 (2019). http://www.fasebj.org

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Section: Methodsmentioning

confidence: 99%

Zoledronic acid promotes TLR‐4‐mediated M1 macrophage polarization in bisphosphonate‐related osteonecrosis of the jaw

Zhu

et al. 2019

FASEB j.

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“…Recent studies have revealed that stem cells could regulate the expression of specific genes in peripheral tissue cells by exosome-mediated transportation of miRNAs [40]. In this work, we screened a large number of differentially expressed miRNAs by comprehensive deep sequencing analysis of the small RNA profile from exosomes released by BMMSCs.…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow Mesenchymal Stem Cell-derived Exosomes Promote Plasminogen Activator Inhibitor 1 Expression in Vascular Cells in the Local Microenvironment During Rabbit Osteonecrosis of the Femoral Head

Wang

et al. 2020

Preprint

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Background Nontraumatic osteonecrosis of the femoral head (NONFH) is a highly disabling orthopedic disease in young individuals. Plasminogen activator inhibitor 1 (PAI-1) has been reported to be positively associated with NONFH. We aimed to investigate the dysregulating PAI-1 in bone marrow mesenchymal stem cells (BMMSCs) and vascular cells in rabbit steroid-induced NONFH. Methods To verify the hypothesis that BMMSCs could promote thrombus formation in a paracrine manner, we collected exosomes from glucocorticoid-treated BMMSCs (GB-Exo) to determine their regulatory effects on vascular cells. microRNA sequencing was conducted to find potential regulators in GB-Exo. Utilizing gain-of-function and knockdown approaches, we testified regulatory effect of microRNA in exosomes. Results The expression of PAI-1 was significantly increased in local microenvironment of the femoral head in ONFH model. GB-Exo promoted PAI-1 expression in vascular smooth muscle cells and vascular endothelial cells. We also revealed that miR-451-5p in GB-Exo should be responsible for the elevated PAI-1. Moreover, we identified miR-133b-3p and tested its role as an potential inhibitor of PAI-1. Conclusions This study provided considerable evidence for BMMSC exosomal miR-mediated upregulation of the fibrinolytic regulators PAI-1 in vascular cells. The disruption of coagulation and low fibrinolysis in the femoral head will eventually lead to a disturbance in microcirculation of NONFH. We believe that our findings could be of great significance for guiding clinical trials in the future.

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“…Age-related osteoporosis is a complex disease, and in order to study it, physiologically similar models are needed. It has been reported that SD rats more than 9 months old can be used for establishing an age-related bone loss model [27], and previous research has proven that male SD rats would develop osteoporosis naturally with age [28,29]. Therefore, aged SD rats were chosen as a model of senile bone loss in our research.…”

Section: Discussionmentioning

confidence: 99%

The therapeutic effect of secretome from human umbilical cord-derived mesenchymal stem cells in age-related osteoporosis

Liang

Liu

Peng

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Senile osteoporosis is closely related to the loss of function of stem cells. In this study, we tried to investigate the potential of secretome from human umbilical cord-derived mesenchymal stem cells (hUCMSCs) in recovering stem cell ability from senescence and then delaying bone loss. We first harvested bone marrow-derived mesenchymal stem cells (BMSCs) from young and old rats and then compared their cellular characteristics such as cell growth, anti-senescence and differentiation. The results showed that these abilities were negatively affected by animal aging. Subsequently, aged BMSCs were exposed to secretome from hUCMSCs, and we found that this loss of cell potential can be modified by secretome treatment. Thereafter, the secretome was loaded into silk fibroin-based hydrogels and used for an in vivo animal study. The results showed that compared to the old untreated group, the bone formation capacity of aged rats was improved by local treatment of secretome-loaded silk fibroin hydrogels. In conclusion, these findings demonstrated that secretome from hUCMSCs has the capacity to recover stem cell potential and delay local bone loss in age-related osteoporosis, which could potentially be applied in osteoporosis therapy in the future.

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MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

Cited by 177 publications

References 62 publications

Zoledronic acid promotes TLR‐4‐mediated M1 macrophage polarization in bisphosphonate‐related osteonecrosis of the jaw

Zoledronic acid promotes TLR‐4‐mediated M1 macrophage polarization in bisphosphonate‐related osteonecrosis of the jaw

Bone Marrow Mesenchymal Stem Cell-derived Exosomes Promote Plasminogen Activator Inhibitor 1 Expression in Vascular Cells in the Local Microenvironment During Rabbit Osteonecrosis of the Femoral Head

The therapeutic effect of secretome from human umbilical cord-derived mesenchymal stem cells in age-related osteoporosis

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