MAP Kinase Phosphatase-1 Protects against Inflammatory Bone Loss

Sartori, Rafael; Li, F.; Kirkwood, Keith L.

doi:10.1177/0022034509349306

Cited by 62 publications

(84 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Akt stimulation by lico F may contribute to the improvement of impaired glucose intolerance in diet-induced obese mice. The mitogen-activated protein kinase (MAPK) family (p38 MAPK, ERK1/ 2, and JNK) has an important function in the regulation of the proinflammatory cytokines [28]. Recent studies have proposed a potential role of p38 MAPK activation in glucose uptake induced by insulin [29e32].…”

Section: Discussionmentioning

confidence: 99%

Licochalcone F alleviates glucose tolerance and chronic inflammation in diet-induced obese mice through Akt and p38 MAPK

et al. 2016

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Licochalcone F alleviates glucose tolerance and chronic inflammation in diet-induced obese mice through Akt and p38 MAPK

et al. 2016

View full text Add to dashboard Cite

“…The ROI for the bone volume fraction (BVF) and bone mineral density (BMD) analysis was based on several easily identifiable anatomical landmarks. The BFV/BMDs were then calculated using the GE MicroView software's innate bone analysis module Patil et al, 2008;Sartori et al, 2009). All CT scans were measured and assessed by an independent masked examiner in a blinded manner.…”

Section: Methodsmentioning

confidence: 99%

Silencing Mitogen-Activated Protein Kinase-Activated Protein Kinase-2 Arrests Inflammatory Bone Loss

Li¹,

Yu²,

Zinna³

et al. 2010

J Pharmacol Exp Ther

View full text Add to dashboard Cite

p38 mitogen-activated protein kinases (MAPKs) are critical for innate immune signaling and subsequent cytokine expression in periodontal inflammation and bone destruction. In fact, previous studies show that systemic p38 MAPK inhibitors block periodontal disease progression. However, development of p38 MAPK inhibitors with favorable toxicological profiles is difficult. Here, we report our findings regarding the contribution of the downstream p38 MAPK substrate, mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAPK-2), in immune response modulation in an experimental model of pathogen-derived lipopolysaccharide (LPS)-induced periodontal bone loss. To determine whether small interfering RNA (siRNA) technology has intraoral applications, we initially validated MK2 siRNA specificity. Then, gingival tissue surrounding maxillary molars of rats was injected with MK2 siRNA or scrambled siRNA at the palatal regions of bone loss. Intraoral tissues treated with MK2 siRNA had significantly less MK2 mRNA expression compared with scrambled siRNA-treated tissues. MK2 siRNA delivery arrested LPS-induced inflammatory bone loss, decreased inflammatory infiltrate, and decreased osteoclastogenesis. This proof-of-concept study suggests a novel target using an intraoral RNA interference strategy to control periodontal inflammation.

show abstract

“…Studies have shown that MKP-1 KO mice are susceptible to endotoxic shock; exhibited a marked increase in production of proinflammamtory cytokine TNF-α, IL-6, and an anti-inflammatory cytokine IL-10 as compared with WT animals 20 . MKP-1 KO mice also had a marked increase in both the incidence and severity of experimentally induced autoimmune arthritis 21,22 , and exhibited more bone loss after LPS challenge as compared with WT animals 23 . Using an orally-active p38 MAPK inhibitor, we have shown p38 signaling is critical to LPS-induced inflammatory response, osteoclastogenesis, and alveolar bone loss 24 .…”

Section: Introductionmentioning

confidence: 96%

Anti-inflammatory effect of MAPK phosphatase-1 local gene transfer in inflammatory bone loss

Herbert

et al. 2010

Gene Ther

View full text Add to dashboard Cite

Alveolar bone loss associated with periodontal diseases is the result of osteoclastogenesis induced by bacterial pathogens. The mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP- 1) is a critical negative regulator of immune response as a key phosphatase capable of dephosphorylating activated MAPKs. In this study, rat macrophages transduced with recombinant adenovirus (Ad).MKP-1 specifically dephosphorylated activated MAPKs induced by lipopolysaccharide (LPS) compared with control cells. Bone marrow macrophages from MKP-1 knockout (KO) mice exhibited higher interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and select chemokine compared with wild type (WT) mice when stimulated by LPS. In addition, bone marrow cultures from MKP-1 KO mice exhibited significantly more osteoclastogenesis induced by LPS compared with WT mice. Importantly, MKP-1 gene transfer in bone marrow cells of MKP-1 KO mice significantly decreased IL-6, IL-10, TNF-α, chemokine levels and formed fewer osteoclasts induced by LPS compared with control group of cells. Furthermore, MKP-1 gene transfer in an experimental periodontal disease model attenuated bone resorption induced by LPS. Histological analysis confirmed that periodontal tissues transduced with Ad.MKP-1 exhibited less infiltrated inflammatory cells, less osteoclasts and less IL-6 compared with rats of control groups. These studies indicate that MKP-1 is a key therapeutic target to control of inflammation-induced bone loss.

show abstract

MAP Kinase Phosphatase-1 Protects against Inflammatory Bone Loss

Cited by 62 publications

References 27 publications

Licochalcone F alleviates glucose tolerance and chronic inflammation in diet-induced obese mice through Akt and p38 MAPK

Licochalcone F alleviates glucose tolerance and chronic inflammation in diet-induced obese mice through Akt and p38 MAPK

Silencing Mitogen-Activated Protein Kinase-Activated Protein Kinase-2 Arrests Inflammatory Bone Loss

Anti-inflammatory effect of MAPK phosphatase-1 local gene transfer in inflammatory bone loss

Contact Info

Product

Resources

About