Reduced COX-2 Expression in Aged Mice Is Associated With Impaired Fracture Healing

Naik, Amish; Xie, Chao; Zuscik, Michael J.; Kingsley, Paul D.; Schwarz, Edward M.; Awad, Hani A.; Guldberg, Robert E.; Drissi, Hicham; Puzas, J. Edward; Boyce, Brendan F.; Zhang, Xinping; O’Keefe, Regis J.

doi:10.1359/jbmr.081002

Cited by 144 publications

(127 citation statements)

References 69 publications

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“…Naik et al (2009) mentioned that expression of COX-2 during the early inflammatory phase of repair regulates chondrogenesis, bone formation, and remodeling. Huang et al (2014) reported that COX-2-deficient periosteal progenitors present impaired osteogenic and chondrogenic differentiation in cell culture.…”

Section: Discussionmentioning

confidence: 99%

Mucus of Achatina fulica stimulates mineralization and inflammatoryresponse in dental pulp cells

Kantawong

Thaweenan²,

Mungkala³

et al. 2016

Turk J Biol

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IntroductionDental and oral diseases are major concerns in Thailand, affecting the country's health system. Everyone, at any age, is at risk of losing teeth. Tooth loss can lead to many health problems, including difficulty chewing, which increases the risk of poor nutrition. In addition, tooth loss leaves a large gap, leading to plaque accumulation that can cause periodontal disease. Moreover, the remaining teeth start to shift in an attempt to fill in the gap, leading to misalignment of teeth. Losing teeth may also affect personality, including a loss of confidence that may affect work or social activities. Restoration, with dentures or dental implants, is needed to replace the missing teeth.Current research has focused on dental and bone implants capable of promoting cell differentiation Xavier Acasigua et al., 2014;Naddeo et al., 2015). Cells isolated from tooth pulp contain odontoblasts, fibroblasts, immune cells, and undifferentiated mesenchymal cells called dental pulp stem cells (DPSCs). These findings may lead to restoration using dental pulp cells (DPCs), together with dental implants, to replace lost teeth. Various research groups have proposed the possibility of producing bioactive dental implants by adding natural products, such as natural hydroxyapatite/ zircon (Karamian et al., 2014), plant products (Varoni et al., 2012), or herbal extracts (Wang et al., 2012), to dental materials.Snails have been used in medicine since ancient times. Until the late 19th century, the synthetic peptide ziconotide (SNXIII), which is found in the venom of Conus magus, was used as a painkiller following approval by the United States Food and Drug Administration (Bonnemain, 2005). According to reports, snails contain several medically useful substances, including mytimacinlike antimicrobial peptides, which are exclusively found in the mucus of giant African snails (Zhong et al., 2013). In addition, lectin, which acts as an antimicrobial, is also present in the mucus of giant African snails (Ito et al., 2011). High-performance liquid chromatography was used to determine the amount of allantoin and glycolic Abstract: Dental pulp tissue contains stem cells that can be isolated and used for regenerative medicine in tooth restoration or autologous transplantation. The aim of this study was to observe the mineralization and gene expression in dental pulp cells (DPCs) following treatment with snail mucus. Snail mucus was collected from adult Achatina fulica and processed as a dry powder by the freeze-drying technique. The mucus powder was dissolved in a culture medium at a concentration of 15 µg/mL. DPCs were prepared by the outgrowth technique and cultured in a 6-well plate at a density of 5 × 10 4 cells per well. A mucus-supplemented medium (15 µg/mL) was added to each well. Cell culture was maintained for 3 weeks. The results of Alizarin Red S staining indicated that the DPCs cultured in a medium supplemented with snail mucus showed a higher number of mineralized nodules as compared with the control group cultured in a norm...

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Section: Discussionmentioning

confidence: 99%

Mucus of Achatina fulica stimulates mineralization and inflammatoryresponse in dental pulp cells

Kantawong

Thaweenan²,

Mungkala³

et al. 2016

Turk J Biol

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“…[5][6][7][8] The initial fracture hematoma develops immediately after injury and contains various immune cell populations originating from bone marrow, disrupted blood and lymph vessels. 8,17 So far, studies on the early inflammatory phase of fracture healing primarily focused on the infiltration of immune cells into already existing fracture hematomas.…”

Section: Discussionmentioning

confidence: 99%

“…However, the participation of immune cells and soluble factors derived from them are hypothesized to be decisive for tissue repair like wound healing or bone regeneration. [5][6][7][8] Macrophages are critical for the clearance of cell debris and for matrix degradation during tissue regeneration 9 and neutrophil recruitment is important in regard to fighting infections 10 which are more likely to occur in damaged tissues. Depletion of macrophages and the depletion of all T lymphocytes lead to less effective wound healing, while the depletion of CD8 1 T cells exhibits the opposite effect.…”

Section: Introductionmentioning

confidence: 99%

Human immune cells' behavior and survival under bioenergetically restricted conditions in an in vitro fracture hematoma model

et al. 2013

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The initial inflammatory phase of bone fracture healing represents a critical step for the outcome of the healing process. However, both the mechanisms initiating this inflammatory phase and the function of immune cells present at the fracture site are poorly understood. In order to study the early events within a fracture hematoma, we established an in vitro fracture hematoma model: we cultured hematomas forming during an osteotomy (artificial bone fracture) of the femur during total hip arthroplasty (THA) in vitro under bioenergetically controlled conditions. This model allowed us to monitor immune cell populations, cell survival and cytokine expression during the early phase following a fracture. Moreover, this model enabled us to change the bioenergetical conditions in order to mimic the in vivo situation, which is assumed to be characterized by hypoxia and restricted amounts of nutrients. Using this model, we found that immune cells adapt to hypoxia via the expression of angiogenic factors, chemoattractants and pro-inflammatory molecules. In addition, combined restriction of oxygen and nutrient supply enhanced the selective survival of lymphocytes in comparison with that of myeloid derived cells (i.e., neutrophils). Of note, non-restricted bioenergetical conditions did not show any similar effects regarding cytokine expression and/or different survival rates of immune cell subsets. In conclusion, we found that the bioenergetical conditions are among the crucial factors inducing the initial inflammatory phase of fracture healing and are thus a critical step for influencing survival and function of immune cells in the early fracture hematoma.

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“…Particularly, hypoxia exerts a significant influence (Heppenstall et al, 1976), via regulating the expression of transcriptional factors and cytokines (Warren et al, 2001) such as hypoxia-inducible factors (Akeno et al, 2001), vascular endothelial growth factor (Bouletreau et al, 2002) and bone morphogenetic protein 2 (BMP-2) (Bouletreau et al, 2002). And such factors/cytokines then pose regulatory roles on the wound healing or bone regeneration (Naik et al, 2009;Kolar et al, 2010). BMPs, such as BMP-2 (Hu et al, 2013;Gao et al, 2015), alkaline phosphatase (ALP) (Huang et al, 2015), osteopontin (Jiang et al, 2015) and osteocalcin (Huang et al, 2015), have been indicated to be deregulated by hypoxia in the differentiation of MSCs during bone repair.…”

Section: Introductionmentioning

confidence: 99%

N-methyl pyrrolidone (NMP) ameliorates the hypoxia-reduced osteoblast differentiation via inhibiting the NF-κB signaling

Zhao

et al. 2016

J. Toxicol. Sci.

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-Ischemic-hypoxic condition for local osteoblasts and bone mesenchymal stem cells during bone fracture inhibits bone repairing. N-methyl pyrrolidone (NMP) has been approved as a safe and biologically inactive small chemical molecule, and might be useful for bone fracture repairing. In the present study, we investigated the effect of NMP on the hypoxia-reduced cellular viability and the expression of differentiation-associated markers, such as bone morphogenetic protein 2 (BMP-2), propeptide of type I procollagen I (PINP), alkaline phosphatase (ALP) or runt-related transcription factor 2 (Runx2) in the osteoblasts, and then we examined the molecular mechanism underlining such effect in the human osteoblastic hFOB 1.19 cells. Our results demonstrated that NMP significantly blocked the hypoxia-induced cell viability reduction and inhibited the hypoxia-caused expression downregulation of BMP-2, PINP, ALP and Runx2 in hFOB 1.19 cells. Then we confirmed the involvement of nuclear factor κB (NF-κB) pathway in the regulation by NMP on the hypoxia-mediated the reduction of osteoblast differentiation. The upregulated expression and transcriptional activity of NF-κB, while the downregulated inhibitory κB expression by the hypoxia treatment was reversed by the treatment with 10 mM NMP. In conclusion, our study found a protective role of NMP in osteoblast differentiation in response to hypoxia, and such protection was through inhibiting the NF-κB signaling. This suggests that NMP might be a protective agent in bone fracture repairing.

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Reduced COX-2 Expression in Aged Mice Is Associated With Impaired Fracture Healing

Cited by 144 publications

References 69 publications

Mucus of Achatina fulica stimulates mineralization and inflammatoryresponse in dental pulp cells

Mucus of Achatina fulica stimulates mineralization and inflammatoryresponse in dental pulp cells

Human immune cells' behavior and survival under bioenergetically restricted conditions in an in vitro fracture hematoma model

N-methyl pyrrolidone (NMP) ameliorates the hypoxia-reduced osteoblast differentiation via inhibiting the NF-κB signaling

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