Porphyromonas gingivalis-derived Lysine Gingipain Enhances Osteoclast Differentiation Induced by Tumor Necrosis Factor-α and Interleukin-1β but Suppresses That by Interleukin-17A

Akiyama, Tomohito; Miyamoto, Yukio; Yoshimura, Kenichi; Yamada, Atsushi; Miki, Takami; Suzawa, Tetsuo; Hoshino, Mitsunori; Imamura, Takahisa; Akiyama, Chie; Yasuhara, Rika; Mishima, Kenji; Maruyama, Toshifumi; Kohda, Chikara; Tanaka, Kazuo; Potempa, Jan; Yasuda, Hisataka; Baba, Kazuyoshi; Kamijo, Ryutaro

doi:10.1074/jbc.m113.520510

Cited by 43 publications

(35 citation statements)

References 45 publications

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“…Various inflammatory factors, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, are able to stimulate osteoclast differentiation from monocyte-macrophages (7,8). A number of previous studies have reported that infection stimulates the activation of osteoclast differentiation, as well as the molecular mechanisms that trigger it (9,10). However, bone/fracture healing is a proliferative physiological process and requires a lot of new osteoblasts to accelerate the synthesis and calcification of bone, as well as the increase of bone volume and density (11).…”

Section: Introductionmentioning

confidence: 99%

Triptolide inhibits the function of TNF-α in osteoblast differentiation by inhibiting the NF-κB signaling pathway

Liu

Wang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Chronic inflammation often delays fracture healing or leads to bone nonunion. Effectively suppressing pathological inflammation is crucial for fracture healing or bone remodeling. Triptolide, which is a diterpenoid epoxide, is the major active component of the Thunder God Vine, Tripterygium wilfordii. The aim of the present study was to investigate the role of triptolide in osteoblast differentiation and explore the molecular mechanisms of triptolide in fracture healing. Alkaline phosphatase (ALP) activity was used to evaluate osteoblast differentiation. ALP activity was measured via histochemical staining and western blotting was used to determine the expression of factors associated with inflammation. C2C12 cells were initially treated with 200 ng/ml bone morphogenetic protein (BMP)-2 alone for 3 days, which caused a significant increase in ALP activity (P<0.01). However, treatment with tumor necrosis factor (TNF)-α significantly decreased the ALP activity (P<0.05). Notably, treatment with the chronic inflammatory cytokine TNF-α significantly decreased the effect of BMP-2 in C2C12 cells compared with BMP-2 treatment alone (P<0.01). C2C12 cells were treated with increasing concentrations of BMP-2 or TNF-α for 3 days. The results demonstrated that TNF-α treatment significantly inhibited BMP-2-induced osteoblast differentiation in a dose-dependent manner (P<0.01). The role of triptolide in BMP-2-induced osteoblast differentiation was also examined. Cells were treated with BMP-2, BMP-2 + TNF-α alone, or BMP2 + TNF-α with increasing concentrations of triptolide (4, 8 or 16 ng/ml). After 3 days, the results of ALP activity revealed that triptolide significantly reversed the TNF-α-associated inhibition of osteoblast differentiation (P<0.01). Western blotting analysis demonstrated that triptolide markedly inhibited the phosphorylation of nuclear factor-κB, therefore suppressing the effects of TNF-α. In summary, triptolide is able to reverse the TNF-α-associated suppression of osteoblast differentiation, suggesting that triptolide treatment may have a positive effect on bone remodeling and fracture repairing.

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Section: Introductionmentioning

confidence: 99%

Triptolide inhibits the function of TNF-α in osteoblast differentiation by inhibiting the NF-κB signaling pathway

Liu

Wang

et al. 2017

Experimental and Therapeutic Medicine

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“…[49,50] However, in other studies, the association of HSV-1 with chronic periodontitis was not noted.…”

Section: The Role Of Herpesvirus In the Pathogenesis Of Odontogenic Amentioning

confidence: 88%

“…Induction of osteoclastogenesis due to cleavage of osteoprotegerin [30,49] C. rectus LPS: Stimulation of synthesis by gingival prostaglandin fibroblasts е2, il-1 and il-6 [32] Groel: Induces secretion by gingival cells il-6 and il-8 [38,45] T. denticola Chymotrypsin-like protease: Lysis of the components of the intercellular matrix (hyaluronic acid, chondroitin sulfate, fibronectin, laminin, fibrinogen) [16,17] A. actinomycetocomitans 1. Activation TLR-4 and myd88: Stimulation of differentiation of blood monocytes into osteoclasts [22] 2.…”

Section: Discussionmentioning

confidence: 99%

Untitled

Batyrbekova¹

2017

AJP

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Pyoinflammatory diseases of maxillofacial area (MFA) are one of the most serious problems of maxillofacial surgery. The high medical and social significance of these diseases are due to their frequent occurrence in persons of working age and the risk of life-threatening complications: Bleeding from the great vessel, brain abscess, the spread of infection into the deep cellular spatium of the collum. In more than 1/3 of all patients, pyogenic lesions of MFA develop on the background of secondary immunodeficiency, accompanied by impaired regulation of the secretion of pro-inflammatory cytokines, and predisposing to prolonged smoldering flow or, on the contrary, rapid spread of inflammation with extensive tissue damage. This fact determines the importance of developing integrated approaches to diagnostics and treatment. The aim of the study is to generalize modern ideas about causative agents and their effect on the features of the inflammatory diseases of the MFA. We systematized and analyzed contemporary works of Russian and foreign authors on the study of the effects of causative agents of bacterial and viral nature and characteristic changes in the immune status. The modern data on the role of microbial factors in the development and maintenance of local and systemic immunological status disorders in case of inflammatory disease of MFA are presented, the impact on the development of bacterial and viral microflora diseases is given, with special attention paid to immunomodulatory effects of causative agents. The factors of pathogens influence most frequently associated with inflammatory diseases of theMFA and collum, as well as the relationship of individual microorganisms with the clinical manifestations of this pathology type and the detection of the pathogenetic role of immune disorders, allow to conduct studies on the formation of optimal correction schemes for each patient (personified) depending on the features of the course of the disease.

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“…In addition, several reports have indicated that gingipains are involved in alveolar bone loss [2][3][4][5]. Although the mechanisms by which gingipains cause bone resorption have not been elucidated in detail, we found that a secreted form of the lysine-specific gingipain (Kgp) promotes differentiation of osteoclasts, which facilitate bone resorption [6][7][8]. In this review, the role of gingipains in alveolar bone loss during periodontitis is discussed, including our recent findings that Kgp mediates proteolytic degradation of osteoprotegerin (OPG), a protein that inhibits osteoclastogenesis.…”

Section: Introductionmentioning

confidence: 92%

“…We therefore investigated whether gingipains induced osteoclast differentiation in vitro using a co-culture system of mouse osteoblasts and bone marrow cells [6][7][8]. The cells were treated with Kgp and RgpB purified from culture supernatants of P. gingivalis.…”

Section: Kgp But Not Rgpb Enhances Osteoclast Differentiation In Vitromentioning

confidence: 99%

Molecular mechanisms for bone resorption by gingipains: Degradation of osteoprotegerin by lysine-specific gingipain is a key factor for enhanced osteoclastogenesis

Porphyromonas gingivalis-derived Lysine Gingipain Enhances Osteoclast Differentiation Induced by Tumor Necrosis Factor-α and Interleukin-1β but Suppresses That by Interleukin-17A

Cited by 43 publications

References 45 publications

Triptolide inhibits the function of TNF-α in osteoblast differentiation by inhibiting the NF-κB signaling pathway

Triptolide inhibits the function of TNF-α in osteoblast differentiation by inhibiting the NF-κB signaling pathway

Untitled

Molecular mechanisms for bone resorption by gingipains: Degradation of osteoprotegerin by lysine-specific gingipain is a key factor for enhanced osteoclastogenesis

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