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Wen Zhang, Fujian Zhao, Deqiu Huang, Xiaoling Fu, Xian Li, Xiaofeng Chen
Host immune response induced by foreign bone biomaterials plays an important role in determining their fate after implantation. Hence, it is well worth designing advanced bone substitute materials with beneficial immunomodulatory properties to modulate the host-material interactions. Bioactive glasses (BG), with excellent osteoconductivity and osteoinductivity, are regarded as important biomaterials in the field of bone regeneration. In order to explore a novel BG-based osteoimmunomodulatory implant with the capacity of potentially enhancing bone regeneration, it is a possible way to regulate the local immune microenvironment through manipulating macrophage polarization...
October 25, 2016: ACS Applied Materials & Interfaces
Chenyi Ye, Wei Zhang, Shuai Jiang, Yuanbin Yu, Xiaoyu Zhou, Ling Zhu, Deting Xue, Rongxin He
Inflammation and osteoclastogenesis play critical roles in wear-particle-induced periprosthetic osteolysis (WPO). Platelet-derived growth factor-BB (PDGF-BB) could promote osteogenesis and inhibit inflammatory response. The aim of this study was to investigate the impact of PDGF-BB on WPO. Mice were divided into four groups, namely, sham, vehicle, low-, and high-dose PDGF-BB groups. Mice in the rhPDGF-BB groups were treated with PDGF-BB at 0.25 or 1 mg/ml/kg/day. Mice in the sham and vehicle groups received PBS daily...
October 24, 2016: Growth Factors
Erxia Du, Patrick McAllister, Venugopal Reddy Venna, Liping Xiao
Ketamine has been used safely in clinics for decades for analgesia and anesthesia. It is increasingly popular in clinical practice due to its new uses and importance for emergency procedures. It is known that ketamine is sequestered in the bone marrow and the major receptors for ketamine, noncompetitive N-methyl-d-aspartate receptors (NMDARs), are expressed in osteoclasts (OCs) and osteoblasts. However, the impact of ketamine on OCs or osteoblasts is unknown. In this study we investigated the effects of ketamine on osteoclastogenesis and regulation of NMDARs expression in vitro...
October 24, 2016: Journal of Cellular Biochemistry
Sawako Moriwaki, Takeshi Into, Keiko Suzuki, Mutsumi Miyauchi, Takashi Takata, Keigo Shibayama, Shumpei Niida
Chronic inflammation-associated bone destruction, which is observed in rheumatoid arthritis (RA) and periodontitis, is mediated by excessive osteoclastogenesis. We showed previously that γ-glutamyltranspeptidase (GGT), an enzyme involved in glutathione metabolism, acts as an endogenous activator of such pathological osteoclastogenesis, independent of its enzymatic activity. GGT accumulation is clinically observed in the joints of RA patients, and, in animals, the administration of recombinant GGT to the gingival sulcus as an in vivo periodontitis model induces an increase in the number of osteoclasts...
October 24, 2016: Scientific Reports
Shuyu Guo, Yuanyuan Ni, Jingjing Ben, Yang Xia, Tingting Zhou, Dongyue Wang, Jieli Ni, Hui Bai, Lin Wang, Junqing Ma, Qi Chen
Osteoclasts originate from bone marrow monocyte/macrophage lineage cells, which are important for bone health. Class A scavenger receptor (SR-A) is a multifunctional molecule that functions during differentiation of monocyte into macrophages and osteoclasts. To further characterize the role of SR-A in osteoclasts, we used the murine tooth movement model (TM) and the murine anterior cruciate ligament transection model of osteoarthritis (ACLT OA). In these two models the bones involved are of different origin and have different properties...
2016: International Journal of Biological Sciences
Pakchisa Khonsuphap, Prasit Pavasant, Rizky Aditya Irwandi, Chidchanok Leethanakul, Anjalee Vacharaksa
BACKGROUND: Prostaglandin E2 (PGE2) accumulates in inflamed periodontal tissue and induces the receptor activator of nuclear factor kappa-B ligand (RANKL)-RANK-osteoprotegerin (OPG) signaling associated with bone resorption. Although oral epithelial cells maintain tissue homeostasis, the role of these cells in RANKL regulation remains unknown. METHODS: To mimic inflamed condition, RANKL upregulation in human mandibular osteoblast-like cells (HMOBs) were stimulated with PGE2...
October 20, 2016: Journal of Periodontology
Emeline Puissant, Marielle Boonen
Osteoclasts are giant bone-resorbing cells originating from monocytes/macrophages. During their differentiation, they overexpress two lysosomal enzymes, cathepsin K and TRAP, which are secreted into the resorption lacuna, an acidified sealed area in contact with bone matrix where bone degradation takes place. Here we report that the acid hydrolase HYAL1, a hyaluronidase able to degrade the glycosaminoglycans hyaluronic acid (HA) and chondroitin sulfate, is also upregulated upon osteoclastogenesis. The mRNA expression and protein level of HYAL1 are markedly increased in osteoclasts differentiated from RAW264...
2016: PloS One
Bryant R England, Geoffrey M Thiele, Ted R Mikuls
PURPOSE OF REVIEW: This article reviews recent literature on the origin and pathogenic role of anticitrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA). RECENT FINDINGS: ACPAs and ACPA-immune complexes interact with immune cells to facilitate articular inflammation. Findings from recent in vitro and in vivo studies are congruent with epidemiologic observations in RA supporting a pathogenic role of ACPAs. SUMMARY: ACPAs target proteins/peptides with citrullinated epitopes and serve as informative RA biomarkers...
October 13, 2016: Current Opinion in Rheumatology
Zhongyang Lu, Yanchun Li, Colleen W Brinson, Keith L Kirkwood, Maria F Lopes-Virella, Yan Huang
BACKGROUND: We reported that high-fat diet (HFD)-induced metabolic syndrome (MetS) exacerbates lipopolysaccharide (LPS)-stimulated periodontitis and palmitate, the major saturated fatty acid in the HFD, amplified LPS-stimulated gene expression in vitro. Since CD36 is a major receptor for fatty acids, we investigated periodontal CD36 expression in mice with periodontitis and MetS, and the role of CD36 in inflammatory genes in macrophages stimulated by palmitate. METHODS: MetS and periodontitis were induced in mice by HFD and periodontal injection of LPS, respectively...
October 18, 2016: Oral Diseases
Dan Xu, Ying Lyu, Xiaowen Chen, Xiaoyu Zhu, Jinqiu Feng, Yajun Xu
Fructus ligustri Lucidi (FLL) is the fruit of Ligustrum lucidum Ait and a traditional Chinese medicine, primarily known for its role in osteoporosis prevention and treatment. The present study aimed to elucidate the effect and underlying mechanism of action of ethanol extract of FLL on osteoclast differentiation and bone resorption, and to identify the active compounds within it. RAW264.7 murine monocyte/macrophage cells were stimulated with the receptor activator of nuclear factor κB ligand (RANKL) to induce osteoclast differentiation in vitro...
October 13, 2016: Molecular Medicine Reports
Jian-Ying Wang, Ying Yuan, Xiao-Jun Chen, Sheng-Guang Fu, Lei Zhang, Yan-Long Hong, Sheng-Fu You, Yong-Qing Yang
ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia Ulmoides Oliv., a valuable Chinese herb, has shown a variety of health benefits. Despite the widespread clinical use of this herb to treat rheumatoid arthritis (RA) in Traditional Chinese Medicine (TCM), very few studies have described its anti-pathological effects or mechanism in RA. The present study investigated the mechanism of Eucommia Ulmoides Oliv. in an experimental collagen-induced arthritis (CIA) rat model. MATERIALS AND METHODS: The effects of four different Eucommia Ulmoides Oliv...
October 12, 2016: Journal of Ethnopharmacology
Jae Ho Choi, Younho Han, Yong An Kim, Sun Woo Jin, Gi Ho Lee, Hyung Min Jeong, Hyun Sun Lee, Young Chul Chung, Young Chun Lee, Eun Ju Kim, Kwang Youl Lee, Hye Gwang Jeong
Platycodon grandiflorum root-derived saponins (Changkil saponins, CKS) are reported to have many pharmacological activities. In our latest research, CKS was proven to have a significant osteogenic effect. However, the detail molecular mechanism of CKS on osteoclastic differentiation has not been fully investigated. Administration of CKS considerably reduced OVX-induced bone loss, and ameliorated the reduction in plasma levels of alkaline phosphatase, calcium, and phosphorus observed in OVX mice. CKS also repressed the deterioration of bone trabecular microarchitecture...
October 14, 2016: Journal of Cellular Biochemistry
Susannah O'Sullivan, Mei Lin Tay, Jian-Ming Lin, Usha Bava, Karen Callon, Jillian Cornish, Dorit Naot, Andrew Grey
Nilotinib and imatinib are tyrosine kinase inhibitors (TKIs) used in the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). In vitro, imatinib and nilotinib inhibit osteoclastogenesis, and in patients they reduce levels of bone resorption. One of the mechanisms that might underlie these effects is an increase in the production of osteoprotegerin (OPG). In the current work we report that platelet-derived growth factor receptor beta (PDGFRβ) signaling regulates OPG production in vitro...
2016: PloS One
Shangfu Li, Bu Yang, Dian Teguh, Lin Zhou, Jiake Xu, Limin Rong
Osteoporosis and Alzheimer's disease (AD) are common chronic degenerative disorders which are strongly associated with advanced age. We have previously demonstrated that amyloid beta peptide (Aβ), one of the pathological hallmarks of AD, accumulated abnormally in osteoporotic bone specimens in addition to having an activation effect on osteoclast (Bone 2014,61:164-75). However, the underlying molecular mechanisms remain unclear. Activation of NF-κB, extracellular signal-regulated kinase (ERK) phosphorylates, and calcium oscillation signaling pathways by receptor activator NF-κB ligand (RANKL) plays a pivotal role in osteoclast activation...
October 10, 2016: International Journal of Molecular Sciences
Yan Xiu, Wingel Y Xue, Allyn Lambertz, Mariah Leidinger, Katherine Gibson-Corley, Chen Zhao
Previously we have shown that loss of non-canonical NF-κB signaling impairs self-renewal of hematopoietic stem/progenitor cells (HSPCs). This prompted us to investigate whether persistent activation of the non-canonical NF-κB signaling will have supportive effects on HSPC self-renewal. NF-κB-inducing kinase (NIK) is an important kinase that mainly activates the non-canonical pathway through directly phosphorylating IKKα. In contrast to our expectations, constitutive activation of NIK in the hematopoietic system leads to bone marrow failure and postnatal lethality due to intrinsic impairment of HSPC self-renewal and extrinsic disruption of bone marrow microenvironment through enhancing osteoclastogenesis...
October 12, 2016: Stem Cells
Mayu Morita, Shigeyuki Yoshida, Ryotaro Iwasaki, Tetsuro Yasui, Yuiko Sato, Tami Kobayashi, Ryuichi Watanabe, Takatsugu Oike, Kana Miyamoto, Masamichi Takami, Keiko Ozato, Chu-Xia Deng, Hiroyuki Aburatani, Sakae Tanaka, Akihiko Yoshimura, Yoshiaki Toyama, Morio Matsumoto, Masaya Nakamura, Hiromasa Kawana, Taneaki Nakagawa, Takeshi Miyamoto
Bone homeostasis is maintained as a delicate balance between bone-resorption and bone-formation, which are coupled to maintain appropriate bone mass. A critical question is how bone-resorption is terminated to allow bone-formation to occur. Here, we show that TGFβs inhibit osteoclastogenesis and maintain bone-mass through Smad4 activity in osteoclasts. We found that latent-TGFβ1 was activated by osteoclasts to inhibit osteoclastogenesis. Osteoclast-specific Smad4 conditional knockout mice (Smad4-cKO) exhibited significantly reduced bone-mass and elevated osteoclast formation relative to controls...
October 12, 2016: Scientific Reports
Xuan Wen, Xiaogang Li, Yubing Tang, Junzhou Tang, Siru Zhou, Yangli Xie, Jingyuan Guo, Jing Yang, Xiaolan Du, Nan Su, Lin Chen
Chondrogenesis can regulate bone formation. Fibroblast growth factor receptor 3, highly expressed in chondrocytes, is a negative regulator of bone growth. To investigate whether chondrocyte FGFR3 regulates osteogenesis, thereby contributing to postnatal bone formation and bone remodeling, mice with conditional knockout of Fgfr3 in chondrocytes (mutant, MUT) were generated. MUT mice displayed overgrowth of bone with lengthened growth plates. Bone mass of MUT mice was significantly increased at both 1 and 4 months of age...
October 11, 2016: Journal of Biological Chemistry
Shuai Zhao, Yu Sun, Xiaolei Li, Jingcheng Wang, Lianqi Yan, Zhen Zhang, Daxin Wang, Jihang Dai, Jun He, Shuguang Wang
Aseptic prosthetic loosening is a major complication after hip joint replacement. Wear particle-induced periprosthetic osteolysis plays a key role in aseptic prosthetic loosening. Attempting to modulate receptor activator of nuclear factor-κB (RANKL) mediated signaling pathways is a promising strategy to prevent aseptic prosthetic loosening. In the present study, we determined the effect of scutellarin (SCU) on titanium (Ti) particle-induced osteolysis in a mouse calvarial model and RANKL-mediated osteoclastogenesis...
October 8, 2016: International Immunopharmacology
Jumpei Teramachi, Yuji Inagaki, Hiroki Shinohara, Hirohiko Okamura, Di Yang, Kazuhiko Ochiai, Ryoko Baba, Hiroyuki Morimoto, Toshihiko Nagata, Tatsuji Haneji
OBJECTIVE: In the present study, we aimed to clarify the precise mechanism underlying LPS-induced osteoclastogenesis in periodontal disease with a special reference to PKR. MATERIAL AND METHODS: We dissected the role of PKR in LPS-induced osteoclast differentiation and function using primary mouse bone marrow cells and RAW264.7 preosteoclastic cell line. We used a rat experimental periodontitis (PD) model induced by ligature placement with a Porphyromonas gingivalis LPS injection (PD rat), and analyzed the therapeutic effects of C16, a PKR inhibitor, on bone loss in PD rats...
October 8, 2016: Oral Diseases
Serra Ucer, Srividhya Iyer, Ha-Neui Kim, Li Han, Christine Rutlen, Kelly Allison, Jeff D Thostenson, Rafael de Cabo, Robert L Jilka, Charles O'Brien, Maria Almeida, Stavros C Manolagas
Old age and sex steroid deficiency are the two most critical factors for the development of osteoporosis. It remains unknown, however, whether the molecular culprits of the two conditions are similar or distinct. We show herein that at 19.5 months of age - a time by which the age-dependent decline of cortical and cancellous bone mass and cortical porosity were fully manifested in C57BL/6J mice - these animals remained functionally estrogen sufficient. Transgenic mice with conditional expression of mitochondria-targeted catalase - a potent H2 O2 inactivating enzyme - in cells of the myeloid lineage (mitoCAT;LysM-Cre mice), were protected from the loss of cortical, but not cancellous, bone caused by gonadectomy in either sex...
October 7, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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