Aging, inflammation, stem cells, and bone healing

Gibon, Emmanuel; Lu, Laura; Goodman, Stuart B.

doi:10.1186/s13287-016-0300-9

Cited by 184 publications

(131 citation statements)

References 68 publications

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“…Emerging evidence supports the hypothesis that accumulation of senescent cells or alteration of some age‐related molecules (e.g., miRNA, RNA, lipids, and proteins) packaged by exosomes in the bone microenvironment is the primary cause of osteoporosis (Farr et al., 2017; Gibon, Lu, & Goodman, 2016; Lim et al., 2017; Sui, Hu, Zheng, & Jin, 2016; Williams, Smith, Kumar, Vijayan, & Reddy, 2017). Targeting these exosomes, which act as important communicators between cells, may emerge as a new therapeutic approach for osteoporosis (Liu et al., 2017; Long et al., 2017; Nakano et al., 2016).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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The alteration of age‐related molecules in the bone marrow microenvironment is one of the driving forces in osteoporosis. These molecules inhibit bone formation and promote bone resorption by regulating osteoblastic and osteoclastic activity, contributing to age‐related bone loss. Here, we observed that the level of microRNA‐31a‐5p (miR‐31a‐5p) was significantly increased in bone marrow stromal cells (BMSCs) from aged rats, and these BMSCs demonstrated increased adipogenesis and aging phenotypes as well as decreased osteogenesis and stemness. We used the gain‐of‐function and knockdown approach to delineate the roles of miR‐31a‐5p in osteogenic differentiation by assessing the decrease of special AT‐rich sequence‐binding protein 2 (SATB2) levels and the aging of BMSCs by regulating the decline of E2F2 and recruiting senescence‐associated heterochromatin foci (SAHF). Notably, expression of miR‐31a‐5p, which promotes osteoclastogenesis and bone resorption, was markedly higher in BMSCs‐derived exosomes from aged rats compared to those from young rats, and suppression of exosomal miR‐31a‐5p inhibited the differentiation and function of osteoclasts, as shown by elevated RhoA activity. Moreover, using antagomiR‐31a‐5p, we observed that, in the bone marrow microenvironment, inhibition of miR‐31a‐5p prevented bone loss and decreased the osteoclastic activity of aged rats. Collectively, our results reveal that miR‐31a‐5p acts as a key modulator in the age‐related bone marrow microenvironment by influencing osteoblastic and osteoclastic differentiation and that it may be a potential therapeutic target for age‐related osteoporosis.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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“…These changes may involve both innate and acquired immunity as well (Hajishengallis 2010). This is clearly an emerging field, and several immune functions seem to be altered in association with ageing (Gibon et al 2016). However, we will not extend in this topic as it will be reviewed extensively in a related article within this series (Preshaw and Conrads, Journal of Clinical Periodontology, 2017).…”

Section: The Complex Relationship Between Periodontal Tissue Destructmentioning

confidence: 99%

Ageing, dental caries and periodontal diseases

López

Göstemeyer

et al. 2017

J Clinic Periodontology

191

138

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Aim: To review the burden of caries and periodontitis in the elderly, changes with age that can explain this burden, and the vulnerability to disease of elderly populations. Methods: An assessment of surveys in two populations was conducted. Indicators for caries were identified by updating a systematic review. Secular trends for smoking and type 2 diabetes were discussed. Results: Changes in the susceptibility to periodontitis with age may be explained by exposure to pro-inflammatory conditions and changes in the healing capacity of cells and tissues. Due to accumulated periodontal destruction, the number of surfaces at risk for caries increases. The sequels of restorative treatment contribute to an increased susceptibility for caries development. Population-based surveys in the United States and Germany demonstrate a high caries experience among elderly people. A comparison of surveys demonstrates a relative improvement of periodontal health among elderly during the last few decades. Nevertheless, prevalence estimates for periodontitis remain high. Risk indicators for root caries include caries experience, the number of surfaces at risk and poor oral hygiene. Secular trends of main risk factors for periodontitis and their likely influence on the future periodontitis burden in the elderly are discussed. Conclusion: Caries and periodontitis burden in the elderly remain high.

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“…As individuals age, however, these important hallmarks of bone homeostasis are disturbed by mechanisms that are not fully understood. In addition to the increased risk of skeletal complications such as bone fragility and greater fracture risk due to osteoporosis (Gibon et al, 2016), the healing potential of fractures in the elderly is also decreased, as previously shown (Leucht et al, 2013; Leucht et al, 2007). This decreased healing capacity of fractures in the elderly may be attributed to a decreased number of osteoprogenitor cells and osteoblasts, as well as reduced expression of osteogenic growth factors, altogether culminating in a decreased bone mass (Kusumbe et al, 2014).…”

Section: Introductionmentioning

confidence: 80%

“…With aging, the skeleton weakens, resulting in a significantly increased incidence of fractures, often resulting from low-energy falls. Orthopaedic surgeons are faced with the sequelae of osteoporosis, and any drug or treatment that may decrease this burden would result in a significant improvement of lifestyle and comfort for our aging generations (Gibon et al, 2016). There is a growing demand for development and optimization of therapies that promote faster and more efficient fracture healing, and understanding the main regulators of fracture healing is crucial in such a search for a novel treatment.…”

Section: Discussionmentioning

confidence: 99%

Ecto-5′-nucleotidase (CD73) regulates bone formation and remodeling during intramembranous bone repair in aging mice

et al. 2017

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Ecto-5′-nucleotidase (CD73) generates adenosine, an osteoblast activator and key regulator of skeletal growth. It is unknown, however, if CD73 regulates osteogenic differentiation during fracture healing in adulthood, and in particular how CD73 activity regulates intramembranous bone repair in the elderly by using a CD73 knock-out (CD73−/−) mouse model. Monocortical tibial defects were created in 46 to 52-week-old wild type (WT) and CD73−/− mice. Injury repair was analyzed at post-operative days 5, 7, 14 and 21 by micro-computed tomography (micro-CT), histomorphometry, proliferating cell nuclear antigen (PCNA) immunostaining, alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) histochemistry. Aged CD73 knock-out mice exhibited delayed bone regeneration and significantly reduced bone matrix deposition during bone healing detected by histomorphometry and micro-CT. Cell proliferation, ALP activity and osteoclast number were reduced in the CD73−/− mice, suggesting a combined defect in bone formation and resorption due the absence of CD73 activity in this model of intramembranous bone repair. Results from this study demonstrate that osteoblast activation through CD73 activity is essential during bone repair in aged mice, and it may present a drugable target for future biomimetic therapeutic approaches that aim at enhancing bone formation in the elderly patients.

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Aging, inflammation, stem cells, and bone healing

Cited by 184 publications

References 68 publications

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

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

Ageing, dental caries and periodontal diseases

Ecto-5′-nucleotidase (CD73) regulates bone formation and remodeling during intramembranous bone repair in aging mice

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