Hypomethylation in the promoter region of ZPBP as a potential litter size indicator in Berkshire pigs.

In pigs, litter size is typically defined as the total number of piglets born (TNB) or the number of piglets born alive (NBA). Increasing pig litter size is of great economic interest as a means to increase productivity. The capacity of the uterus is a critical component of litter size and may play a central role in prolificacy. In this study, we investigated litter-size-related epigenetic markers in uterine tissue from Berkshire pigs with smaller litter size groups (SLGs) and larger litter size groups (LLGs) using genome-wide bisulfite sequencing (GWBS). A total of 3269 differentially methylated regions (DMRs) were identified: 1566 were hypermethylated and 1703 hypomethylated in LLG compared to SLG. The zona pellucida binding protein (ZPBP) gene was significantly hypomethylated in the LLG promoter region, and its expression was significantly upregulated in uterine tissue. Thus, the methylation status of ZPBP gene was identified as a potential indicator of litter size. Furthermore, we verified its negative correlation with litter size traits (TNB and NBA) in whole blood samples from 172 Berkshire sows as a blood-based biomarker by a porcine methylation-specific restriction enzyme polymerase chain reaction (PMP) assay. The results suggest that the methylation status of the ZPBP gene can serve as a valuable epigenetic biomarker for hyperprolific sows.

Identification of a Bromodomain-containing Protein 2 (BRD2) Gene Polymorphic Variant and Its Effects on Pork Quality Traits in Berkshire Pigs.

Bromodomain-containing protein 2 (BRD2) is a nuclear serine/threonine kinase involved in transcriptional regulation. We investigated the expression and association of the BRD2 gene as a candidate gene for meat quality traits in Berkshire pigs. BRD2 mRNA was expressed at relatively high levels in muscle tissue. Statistical analysis revealed that the c.1709G>C polymorphism of the BRD2 gene was significantly associated with carcass weight, meat color (a*, redness), protein content, cooking loss, water-holding capacity, carcass temperatures 4, 12 and 24 h postmortem, and the 24 h postmortem pH in 384 Berkshire pigs. Therefore, this polymorphism in the porcine BRD2 gene may be used as a candidate genetic marker to improve meat quality traits in pigs.

Association of High-Risk Drinking with Metabolic Syndrome and Its Components in Elderly Korean Men: The Korean National Health and Nutrition Examination Survey 2010-2012.

BACKGROUND: Previous studies have examined the association between alcohol consumption and metabolic syndrome (MetS) in adults, but studies in the elderly are lacking. We examined the relationship between high-risk alcohol consumption and MetS in elderly Korean men using the Alcohol Use Disorders Identification Test (AUDIT) questionnaire from the 2010-2012 Korean National Health and Nutrition Examination Survey. METHODS: Among 25,534 subjects, 2,807 were men >60 years of age; after exclusions, we included 2,088 men in the final analysis. We categorized the study participants into three groups according to AUDIT score: low risk (0-7), intermediate risk (8-14), and high risk (≥15 points). RESULTS: Among the study population, 17.0% of the men were high-risk drinkers, who had the highest mean waist circumference, systolic and diastolic blood pressure (BP), fasting plasma glucose (FPG), and triglyceride (TG) levels. The overall prevalence of MetS was 41.9% in the elderly men, and it was significantly higher in the group with high (48.3%) versus low (31.9%) AUDIT scores. The prevalence of MetS components (elevated BP, high FPG, high TG, and low high-density lipoprotein cholesterol) was associated with a high AUDIT score. The odds ratios (95% confidence interval) of the high-risk group for MetS, elevated BP, and high TG were 1.40 (1.03-1.89), 1.82 (1.28- 2.60), and 1.77 (1.30-2.41) after adjustment for confounding variables. CONCLUSION: AUDIT score was correlated with most MetS components in elderly Korean men.

Association of single-nucleotide polymorphisms in NAT9 and MAP3K3 genes with litter size traits in Berkshire pigs.

Litter size is an economically important trait in the pig industry. We aimed to identify genetic markers associated with litter size, which can be used in breeding programs for improving reproductive traits. Single-nucleotide polymorphisms (SNPs) of Berkshire pigs in the N-acetyltransferase 9 (NAT9) and Mitogen-activated protein kinase kinase kinase 3 (MAP3K3) genes were from RNA sequencing results, and already exist in the databank (NCBI), and were confirmed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). A total of 272 Berkshire sows were used to examine the genotype, and their association with litter size traits was analyzed. The NAT9 SNP was located in chromosome 12 exon 640 mRNA (A  >  G) and the MAP3K3 SNP was located in chromosome 12 intron 11 (80, C  >  T). Association analysis indicated that the GG genotype of NAT9 and the CT genotype of MAP3K3 had the highest values for litter size traits. The GG genotype expressed higher levels of NAT9 mRNA in the endometrium than the other genotypes did, and a positive correlation was found between litter size traits and NAT9, but not MAP3K3 expression level. These results indicate that the NAT9 and MAP3K3 can be used as candidate genes applicable in breeding program for the improvement of litter size traits in Berkshire pigs.

Effect of Single Nucleotide Polymorphisms in IGFBP2 and IGFBP3 Genes on Litter Size Traits in Berkshire Pigs.

Litter size is among the most important traits in swine breeding. However, information on the genetics of litter size in pigs is lacking. In this study, we identified single nucleotide polymorphisms (SNPs) in the insulin-like growth factor binding protein 2 and 3 (IGFBP2 and IGFBP3) genes in Berkshire pigs and analyzed their association with litter size traits. The IGFBP2 SNP was located on chromosome 15 intron 2 (455, A > T) and the IGFBP3 SNP was on chromosome 18 intron 2 (53, A > G). The AT type of IGFBP2 and the GG type of IGFBP3 had the highest values for all litter size traits including total number born (TNB), number of pigs born alive, and breeding value according to TNB. Homozygous GG pigs expressed higher levels of IGFBP3 mRNA in the endometrium than pigs of other genotypes, and a positive correlation was observed between litter size traits and IGFBP3 but not IGFBP2 expression level. These results suggest that SNPs in the IGFBP2 and the IGFBP3 gene are useful biomarkers for increasing the reproductive productivity of Berkshire pigs.

Squalene epoxidase plays a critical role in determining pig meat quality by regulating adipogenesis, myogenesis, and ROS scavengers.

In mammals, Squalene epoxidase (SQLE) is an enzyme that converts squalene to 2,3-oxidosqualene, in the early stage of cholesterol generation. Here, we identified single nucleotide polymorphisms (SNPs) in the SQLE gene (c.2565 G > T) by RNA Sequencing from the liver tissue of Berkshire pigs. Furthermore, we found that homozygous GG pigs expressed more SQLE mRNA than GT heterozygous and TT homozygous pigs in longissimus dorsi tissue. Next, we showed that the SNP in the SQLE gene was associated with several meat quality traits including backfat thickness, carcass weight, meat colour (yellowness), fat composition, and water-holding capacity. Rates of myogenesis and adipogenesis induced in C2C12 cells and 3T3-L1 cells, respectively, were decreased by Sqle knockdown. Additionally, the expression of myogenic marker genes (Myog, Myod, and Myh4) and adipogenic marker genes (Pparg, Cebpa, and Adipoq) was substantially downregulated in cells transfected with Sqle siRNA. Moreover, mRNA expression levels of ROS scavengers, which affect meat quality by altering protein oxidation processes, were significantly downregulated by Sqle knockdown. Taken together, our results suggest the molecular mechanism by which SNPs in the SQLE gene can affect meat quality.

DNA methylation patterns and gene expression associated with litter size in Berkshire pig placenta.

Increasing litter size is of great interest to the pig industry. DNA methylation is an important epigenetic modification that regulates gene expression, resulting in livestock phenotypes such as disease resistance, milk production, and reproduction. We classified Berkshire pigs into two groups according to litter size and estimated breeding value: smaller (SLG) and larger (LLG) litter size groups. Genome-wide DNA methylation and gene expression were analyzed using placenta genomic DNA and RNA to identify differentially methylated regions (DMRs) and differentially expressed genes (DEGs) associated with litter size. The methylation levels of CpG dinucleotides in different genomic regions were noticeably different between the groups, while global methylation pattern was similar, and excluding intergenic regions they were found the most frequently in gene body regions. Next, we analyzed RNA-Seq data to identify DEGs between the SLG and LLG groups. A total of 1591 DEGs were identified: 567 were downregulated and 1024 were upregulated in LLG compared to SLG. To identify genes that simultaneously exhibited changes in DNA methylation and mRNA expression, we integrated and analyzed the data from bisulfite-Seq and RNA-Seq. Nine DEGs positioned in DMRs were found. The expression of only three of these genes (PRKG2, CLCA4, and PCK1) was verified by RT-qPCR. Furthermore, we observed the same methylation patterns in blood samples as in the placental tissues by PCR-based methylation analysis. Together, these results provide useful data regarding potential epigenetic markers for selecting hyperprolific sows.

Associations of the Polymorphisms in DHRS4, SERPING1, and APOR Genes with Postmortem pH in Berkshire Pigs.

Postmortem pH is a main factor influencing the meat quality in pigs. This study investigated the association of postmortem pH with single-nucleotide polymorphisms (SNPs) in the fourth member of the short-chain dehydrogenase/reductase family (DHRS4), the first member of serpin peptidase inhibitor, clade G (complement inhibitor) (SERPING1), and the apolipoprotein R precursor (APOR) genes in Berkshire pigs. The study included 437 pigs, and genotyping was conducted using the GoldenGate Assay (Illumina, San Diego, CA, USA). DHRS4, SERPING1, and APOR polymorphisms were significantly associated with pH45 or pH24 (p < 0.05). SERPING1 was also statistically significantly associated with water holding capacity (p < 0.05), which is closely associated with postmortem pH. These results suggest that SNPs in the DHRS4, SERPING1, and APOR genes have potential for use as genetic markers for the meat quality in pigs.

The rs196952262 Polymorphism of the AGPAT5 Gene is Associated with Meat Quality in Berkshire Pigs.

High-quality meat is of great economic importance to the pig industry. The 1-acylglycerol-3-phosphate-O-acyltransferase 5 (AGPAT5) enzyme converts lysophosphatidic acid to phosphatidic acid in the mitochondrial membrane. In this study, we found that the porcine AGPAT5 gene was highly expressed in muscle tissue, influencing meat characteristics, and we also identified a non-synonymous single-nucleotide polymorphism (nsSNP) (rs196952262, c.673 A>G) in the gene, associated with a change of isoleucine 225 to valine. The presence of this nsSNP was significantly associated with meat color (lightness), lower cooking loss, and lower carcass temperatures 1, 4, and 12 h after slaughter (items T1, T4, and T12 on the recognized quality scale, respectively), and tended to increase backfat thickness and the water-holding capacity. These results suggest that nsSNP (c.673A>G) of the AGPAT5 gene is a potential genetic marker of high meat quality in pigs.

Identification of Differentially Expressed Genes Associated with Litter Size in Berkshire Pig Placenta.

Improvement in litter size has become of great interest in the pig industry because fecundity is directly related to sow reproductive life. Improved reproduction has thus been achieved by elucidating the molecular functions of genes associated with fecundity. In the present study, we identified differentially expressed genes (DEGs) via transcriptomic analysis using RNA-sequencing (RNA-Seq) in Berkshire pig placentas from larger (LLG, mean litter size >12) and smaller (SLG, mean litter size < 6.5) litter size groups. In total 588 DEGs were identified (p < 0.05, > 1.5-fold change), of which 98 were upregulated, while 490 were downregulated in the LLG compared with the SLG. Gene Ontology (GO) enrichment was also performed. We concluded that 129 of the 588 DEGs were closely related to litter size according to reproduction related genes selected based on previous reports, as 110 genes were downregulated and 19 upregulated in the LLG compared with the SLG. RT-qPCR utilizing specific primers targeting the early growth response 2 (EGR2), pheromaxein c subunit (PHEROC) and endothelial lipase (LIPG) genes showed high accordance with RNA-Seq results. Furthermore, we investigated the upstream regulators of these three genes in the placenta. We found that WNT9B, a Wnt signaling pathway molecule, and IL-6, known inducers of EGR2 and LIPG, respectively, were significantly increased in LLG compared with SLG. We believe that the induction of IL-6 and LIPG may play an important role in increasing nutrition supply through the placenta from the sow to the piglet during gestation. These results provide novel molecular insights into pig reproduction.

Single-Nucleotide Polymorphisms in Pig EPHX1 Gene are Associated with Pork Quality Traits.

Epoxide hydrolase 1 (EPHX1) plays an important role in both the activation and detoxification of exogenous chemicals. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that the highest level of EPHX1 expression occurred in Berkshire liver, which is an organ that plays a key role in detoxification. We examined EPHX1 SNPs to analyze effect on increased expression of EPHX1 gene in Berkshire liver by total of 192 pigs of a pure Berkshire line (males = 97; females = 95). As a result, two nonsynonymous SNPs (nsSNPs) of EPHX1 were found from c.685T>G and c.776C > T, and located in 5th and 6th exons, respectively, which constitute the A/b hydrolase 1 domain of epoxide hydrolase. The nsSNP c.685T > G was significant differences in meat color, protein content, collagen content, and pH24 hr. Especially, T and G alleles of the nsSNP c.685T > G were significantly associated with CIE a*/CIE b* and protein content/pH24 hr, respectively. The nsSNP c.776C > T was significant differences in drip loss and protein content. Among meat quality traits to associate with SNPs, the protein content was only significantly associated with sex. Therefore, it is suggested that nsSNP c.685T > G in EPHX1 gene is a potential to apply as appropriate DNA markers for improvement of porcine economic traits.

Canine model of ischemic stroke with permanent middle cerebral artery occlusion: clinical features, magnetic resonance imaging, histopathology, and immunohistochemistry.

The purpose of this study was to identify time-related changes in clinical, MRI, histopathologic, and immunohistochemical findings associated with ischemic stroke in dogs. Additionally, the association of cerebrospinal fluid (CSF) and tissue levels of interleukin (IL)-6 with clinical prognosis was assessed. Ischemic stroke was induced by permanent middle cerebral artery occlusion (MCAO) in nine healthy experimental dogs. The dogs were divided into three groups according to survival time and duration of the experimental period: group A (survived only 1 day), group B (1-week experimental period), and group C (2-week experimental period). Neurologic status was evaluated daily. Magnetic resonance imaging (MRI) was performed according to a predetermined schedule. Concentration of IL-6 in CSF was measured serially after ischemic stroke. Postmortem examination was performed for all experimental dogs. During histopathological examination, variable degrees of cavitation and necrosis due to neuronal cytopathic effects, such as pyknotic nuclei and cytoplasmic shrinkage, were observed on the affected side of the cerebral cortex in all dogs. Immunohistochemistry specific for IL-6 showed increased expression in the ischemic lesions. CSF IL-6 concentrations and ischemic lesion volumes 1 day after ischemic stroke were significantly higher in group A compared to groups B and C.

A study of experimental autoimmune encephalomyelitis in dogs as a disease model for canine necrotizing encephalitis.

In the present study, the use of dogs with experimental autoimmune encephalomyelitis (EAE) as a disease model for necrotizing encephalitis (NE) was assessed. Twelve healthy dogs were included in this study. Canine forebrain tissues (8 g), including white and grey matter, were homogenized with 4 mL of phosphate-buffered saline for 5 min in an ice bath. The suspension was emulsified with the same volume of Freund's complete adjuvant containing 1 mg/mL of killed Mycobacterium tuberculosis H37Ra. Under sedation, each dog was injected subcutaneously with canine brain homogenate at four sites: two in the inguinal and two in the axillary regions. A second injection (booster) was administered to all the dogs using the same procedure 7 days after the first injection. Clinical assessment, magnetic resonance imaging, cerebrospinal fluid analyses, necropsies, and histopathological and immunohistochemical examinations were performed for the dogs with EAE. Out of the 12 animals, seven (58%) developed clinically manifest EAE at various times after immunization. Characteristics of canine EAE models were very similar to canine NE, suggesting that canine EAE can be a disease model for NE in dogs.

Imatinib mesylate plus hydroxyurea chemotherapy for cerebellar meningioma in a Belgian Malinois dog.

An 8-year-old intact male Belgian Malinois, weighing 37.2 kg, was referred for evaluation due to right side facial paresis, ataxia and a 2-month history of decreased cognitive ability. Physical and neurological examinations revealed mild depression, left-sided head tilt, right-sided facial paresis and ataxia. A well-demarcated, broad-based cerebellar mass and hyperostosis were found on CT imaging of the brain. Based on these CT findings, a cerebellar meningioma was strongly suspected. Hydroxyurea and prednisolone were administered; after 4 weeks, there was reduction in mass size as compared to initial CT results. However, the mass size was found to have grown 6 weeks after hydroxyurea treatment. We then prescribed a combination of imatinib mesylate and hydroxyurea. Two weeks following combination treatment, the mass size had reduced significantly. The mass continuously decreased in size until the patient died during anesthesia. Cerebellar transitional meningioma was confirmed by histopathologic examination. To the author's knowledge, this is the first reported case of imatinib mesylate plus hydroxyurea therapy for the treatment of meningioma in veterinary medicine.

A case of gastric adenocarcinoma in a Shih Tzu dog: successful treatment of early gastric cancer.

A 9-year-old castrated male Shih Tzu dog was referred to us, because of chronic vomiting. The patient's hematological, radiographic, ultrasonographic, endoscopic and histological examinations were evaluated for diagnosis. Hematologic analysis indicated moderate anemia and azotemia. Based on the imaging studies, an oval-shaped mass was identified in the gastric pylorus area. A proliferative mass was found on endoscopic examination, and we performed biopsy using grasping forceps. The histopathological findings of the biopsy specimens indicated hypertrophic gastritis, and Y-U pyloroplasty was performed. However, histopathological examination of the surgically resected mass revealed tubular adenocarcinoma of the stomach. Then, carboplatin chemotherapy was performed 4 times for 13 weeks. Clinical signs, such as vomiting, were resolved gradually after surgery and chemotherapy, and the patient's condition was managed favorably until recently (30 months after surgery). This case report describes clinical features, imaging studies, endoscopic characteristics and histopathological and immunohistochemical features of gastric tubular adenocarcinoma as early gastric cancer in a dog.

Unsuccessful cyclosporine plus prednisolone therapy for autoimmune meningoencephalitis in three dogs.

A 4-year-old female Maltese (case 1), a 9-year-old castrated male shih tzu (case 2) and 2-year-old female Pomeranian (case 3) presented with neurological signs, such as head tilt, ataxia, circling and paresis. The three cases were tentatively diagnosed as having meningoencephalitis of unknown etiology based on computed tomography scan and cerebrospinal fluid analysis. All patients were managed with cyclosporine plus prednisolone therapy. The survival times of the three patients were 170, 70 and 21 days, respectively. After the cases died, we performed necropsy and histopathological examination for definitive diagnosis. Based on the necropsy, histopathological and immunohistochemical examinations, cases 1, 2 and 3 were definitely diagnosed as having necrotizing meningoencephalitis, necrotizing leukoencephalitis and granulomatous meningoencephalitis, respectively. This case report demonstrated the clinical findings, brain CT characteristics and histopathological and immunohistochemical features of NME, NLE and GME in dogs and discussed the reason for the relatively short survival times under cyclosporine plus prednisolone therapy.

Mitogen- and stress-activated protein kinase 1 activates osteoclastogenesis in vitro and affects bone destruction in vivo.

Mitogen- and stress-activated protein kinase (MSK) 1 is an important regulator of immune response and mitogenic signaling. In this study, we report for the first time that MSK1 was activated by the osteoclast differentiation factor receptor activator of nuclear factor kappa B ligand (RANKL) in osteoclast precursor cells. Inhibition of upstream kinases ERK1/2 and p38, but not JNK, suppressed MSK activation upon RANKL stimulation. An MSK1 inhibitor efficiently prevented the induction of c-Fos and NFATc1 and CREB phosphorylation by RANKL. Inhibition of MSK1 also successfully blocked RANKL-induced osteoclastogenesis. MSK knockdown with small interfering RNA significantly inhibited osteoclast differentiation and bone resorption. MSK1 did not affect osteoclast survival. The induction of c-Fos and NFATc1 and the phosphorylation of CREB and ATF2 were also inhibited by MSK1 knockdown. Moreover, knockdown of MSK1 significantly blocked recruitment of c-Fos to the NFATc1 promoter upon RANKL stimulation. Therefore, NFATc1-inducible osteoclast-specific genes were downregulated by MSK1 blockade. NFATc1 retrovirus transduction almost completely rescued the differentiation defect of MSK1-silenced cells. In vivo knockdown of MSK1 reduced RANKL-induced bone resorption as well as osteoclast formation. Thus, our results suggested that MSK1 is an important novel molecule involved in RANKL signaling and osteoclast differentiation.

TLT-1s, alternative transcripts of triggering receptor expressed on myeloid cell-like transcript-1 (TLT-1), Inhibits the triggering receptor expressed on myeloid cell-2 (TREM-2)-mediated signaling pathway during osteoclastogenesis.

Triggering receptor expressed on myeloid cells (TREM)-like transcript-1 (TLT-1) is an immunoreceptor tyrosine-based inhibitory motif (ITIM)-baring TREM family protein. In this study, we identified an alternative transcript form of TLT-1, namely TLT-1s, which has very short extracellular immunoglobulin domain consisting of only 202 amino acids. TLT-1s was mainly expressed in macrophages and osteoclast precursor cells. Upon receptor activator of nuclear factor-κB ligand stimulation, TLT-1s mRNA and protein levels were gradually decreased in BMMs. We also showed the TLT-1s is localized to the cytoplasmic membrane in osteoclast precursor cells. TLT-1s silencing strongly enhanced the formation and resorption activity of osteoclast. In addition, forced expression of TLT-1s showed reduced formation of osteoclast. Because ITIM-baring proteins inhibit immunoreceptor tyrosine-based activation motif (ITAM)-mediated receptor signaling, we tested whether TLT-1s physically interacted with TREM-2, the ITAM-associated co-stimulatory receptor essential for osteoclast differentiation. We showed that TLT-1s is associated with TREM-2 in osteoclast precursor cells. TLT-1s is also associated with tyrosine Src homology 2 domain-containing phosphatase-1 and SH2 domain-containing inositol phosphatase-1 and recruited them to the TREM2-ITAM signaling complex. In addition, knockdown of TLT-1s markedly elevated the intracellular calcium concentration and oscillation in osteoclast precursor cells. In addition, calcium-mediated induction of nuclear factor of activated T cells was also increased by TLT-1s silencing. Furthermore, TREM-2-mediated Akt activation and proliferation of osteoclast precursor cells were also enhanced in TLT-1s silenced cells. In this paper, we found the noble ITIM-baring inhibitory membrane protein; TLT-1s, which regulates ITAM-mediated signaling on osteoclastogenesis.

AWP1 binds to tumor necrosis factor receptor-associated factor 2 (TRAF2) and is involved in TRAF2-mediated nuclear factor-kappaB signaling.

Tumor necrosis factor receptor-associated factor 2 (TRAF2) is an adaptor protein which involves in the activation of the transcription factor, nuclear factor kappaB (NF-κB), in the tumor necrosis factor (TNF) receptor pathway. This signaling is modulated by proteins that interact with tumor necrosis factor receptor-associated factor 2. In this study, we identified the zinc-finger protein AWP1 as a tumor necrosis factor receptor-associated factor 2-interacting protein through yeast two-hybrid screening. We found that AWP1 directly interacted with the C-terminal tumor necrosis factor receptor-associated factor (TRAF) domain of tumor necrosis factor receptor-associated factor 2. Knockdown of AWP1 using small hairpin RNA significantly decreased nuclear factor kappaB activity but increased tumor necrosis factor alpha (TNFα)-induced apoptosis, presumably by decreasing the induction of nuclear factor kappaB-responsive anti-apoptotic molecules, including FICE-like inhibitory protein (FLIP), X-linked inhibitor of apoptosis protein (XIAP), Bcl-2, and Bcl-xL. In contrast, overexpression of wild-type AWP1 inhibited nuclear factor kappaB activation. Detailed domain mapping experiments showed that the AN1 domain of AWP1 mediated the functional interaction with tumor necrosis factor receptor-associated factor 2, and the A20 domain was responsible for the negative regulation of nuclear factor kappaB activation. Importantly, ectopic AWP1 overexpression led to an A20 domain-dependent increase in K-48 ubiquitination of tumor necrosis factor receptor-associated factor 2. These data indicate that AWP1 binds to tumor necrosis factor receptor-associated factor 2 and that regulates tumor necrosis factor alpha-induced nuclear factor kappaB activation through two distinct domains.

CXCL2 mediates lipopolysaccharide-induced osteoclastogenesis in RANKL-primed precursors.

The strong inflammatory agent lipopolysaccharide (LPS) has been shown to cause bone lysis in vivo. However, the etiology of LPS-induced bone destruction is still elusive. Here, we show that LPS stimulates the induction of CXCL2 in bone marrow macrophages (BMMs), osteoclast precursors, at the transcription level even in the absence of the synthesis of new proteins including interferon ß. Reactive oxygen species were involved in the secretion of CXCL2 but not in the mRNA expression. CXCL2 mRNA induction by LPS was mediated by p38, JNK, and NFκB signaling pathways. Moreover, c-Fos and p65 were directly recruited to CXCL2 promoter. The conditioned medium from LPS-treated BMMs could enhance migration of osteoclast precursors, which was blocked by treatment with CXCL2-neutralizing antibody or CXCR2 receptor antagonist. The blockade of CXCL2 also reduced LPS-induced osteoclastogenesis. More significantly, CXCL2-neutralization prevented bone destruction in mice treated with LPS. Therefore, CXCL2 might be a useful therapeutic target for inflammatory bone destructive diseases.