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Lipid metabolic disorders are commonly encountered in clinical practice. Dyslipidemia and its prevalence rate are strongly associated with the morbidity and mortality of cardiovascular disease worldwide. We conducted a genetic analysis to determine the association between genetic polymorphisms of the ABO gene in adults middle-aged (40~69 years) with dyslipidemia in the Korean population. A total of 6,750 subjects from the Korea Association REsource (KARE) were selected for this study. Using the genetic and epidemiologic data of 4,403 dyslipidemia cases and 2,347 normal controls from the KARE, single nucleotide polymorphisms (SNPs) in ABO gene were analyzed for their genetic correlation. Eleven SNPs out of the ABO gene demonstrated a statistically significant association with dyslipidemia. Among them, rs8176707 in ABO gene statistically showed the most significant correlation with dyslipidemia (P-value=0.002, odds ratio=0.82, 95% confidence interval=0.78~0.86). The minor allele of T polymorphism within the ABO intron genetic region was associated with a decreased risk of dyslipidemia. This study uncovered a significant association between genetic polymorphism in the ABO gene and dyslipidemia. This finding suggest that ABO SNPs markers have a genetic correlation with the etiology of dyslipidemia.

Since the coronavirus disease-2019 (COVID-19) outbreak, it has been generally believed that a medical technologists (MTs) are supposed to perform polymerase chain reaction tests and next-generation sequencing (NGS) in the hospitals. However, many do not recognize that the duty of MT for clinical genetic testing has not been stated in the Medical Laws (72.5% for MT, N=200; 62.8% for students, N=123). In this regard, to evaluate the feasibility of MT’s role for NGS genetic testing, we requested our subjects to fill out an online survey and analyzed the data. Among them, it shows that the scope of MT’s role, including NGS performance should include clinical genetic testing (99.5% for MT, N=200; 86.8% for students, N=123). Also, questions on clinical genetics, which is associated with both cellular genetics and molecular genetic questions should be included in the National MT License Problem Bank (97.5% for MT; 71.4% for students). Based on these results, the Korean Association of Medical Technologists needs to cooperate synergically with the Academic Association of Biomedical Laboratory Science with respect to genetic education and legislation for the future benefit of both MTs and students.

Abstract Osteoporosis is a condition characterized by decreased bone mineral density (BMD) and reduced bone strength, leading to an increased risk of fractures. Here, to identify novel risk variants for susceptibility to osteoporosis-related traits, an exome-wide association study is performed with 6,485 exonic single nucleotide polymorphisms (SNPs) in 2,666 women of two Korean study cohorts. The rs2781 SNP in UBAP2 gene is suggestively associated with osteoporosis and BMD with p-values of 6.1 × 10−7 (odds ratio = 1.72) and 1.1 × 10−7 in the case-control and quantitative analyzes, respectively. Knockdown of Ubap2 in mouse cells decreases osteoblastogenesis and increases osteoclastogenesis, and knockdown of ubap2 in zebrafish reveals abnormal bone formation. Ubap2 expression is associated with E-cadherin (Cdh1) and Fra1 (Fosl1) expression in the osteclastogenesis-induced monocytes. UBAP2 mRNA levels are significantly reduced in bone marrow, but increased in peripheral blood, from women with osteoporosis compared to controls. UBAP2 protein level is correlated with the blood plasma level of the representative osteoporosis biomarker osteocalcin. These results suggest that UBAP2 has a critical role in bone homeostasis through the regulation of bone remodeling.

Background Hypertension and osteoporosis are the most common types of health problems. A recent study suggested that the fibroblast growth factor receptor-like protein 1 (FGFRL1) gene in giraffes is the most promising candidate gene that may have direct effects on both the skeleton and the cardiovascular system. Aim Our study purposed to replicate the finding that the FGFR5 gene is related to giraffe-related characteristics (height, hypertension, and osteoporosis), and to assess the associations between genetic variants of the FGFR family and three phenotypes. Subjects and methods An association study was performed to confirm the connections between hypertension, osteoporosis, and height and the FGFR family proteins (FGFR1 to FGFR5). Results We identified a total of 192 genetic variants in the FGFR family and found six SNVs in the FGFR2, FGFR3, and FGFR4 genes that were associated with two phenotypes simultaneously. Also, the FGFR family was found to be involved in calcium signalling, and three genetic variants of the FGFR3 gene showed significant signals in the pituitary and hypothalamus. Conclusion Taken together, these findings suggest that FGFR genes are associated with hypertension, height, and osteoporosis. In particular, the present study highlights the FGFR3 gene, which influences two fundamental regulators of bone remodelling.

The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. T2DM is one of the most common types of diabetes and is caused by increased insulin resistance and reduced insulin secretion. Peroxisome proliferator-activated receptor γ coactivator 1 alpha (PPARGC1A) is a master modulator of mitochondrial biogenesis and of gluconeogenesis in liver. In this study, we analyzed genetic polymorphisms of PPARGC1A gene in a middle-aged Korean population with T2DM. Using the genotype data of 736 T2DM cases and 4544 healthy controls obtained from the Korean Association Resource (KARE), we analyzed genetic correlations between single nucleotide polymorphisms (SNPs) of PPARGC1A and T2DM. Fifteen SNPs of PPARGC1A demonstrated a statistically significant association with T2DM. Of these, rs10212638 exhibited the strongest correlation with T2DM (P-value=0.015, OR=1.29, CI=1.05∼1.59), and the minor G allele of PPARGC1A increased the risk of T2DM. This is the first study to report a significant association between genetic polymorphisms in PPARGC1A and T2DM and suggests that SNPs of PPARGC1A display genetic correlations to the etiology of T2DM.

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme belonging to the kynurenine pathway. IDO activity has been suggested as a potential biomarker for early diagnosis of chronic kidney disease (CKD). The aim of this study was to perform coincident association analysis to gain genetic insights into the correlation between IDO activity and CKD. This study evaluated the association between IDO activity and CKD using the Korea Association REsource (KARE) cohort. Logistic and linear regression were used to analyze CKD and quantitative phenotypes such as IDO and estimated glomerular filtration rate (eGFR). Our results identified 10 single nucleotide polymorphisms (SNPs) that were coincidently associated with both IDO and CKD (p < 0.001). Among them, rs6550842, rs77624055, and rs35651150 were selected as potential candidates after excluding SNPs with insufficient evidence for having an association with IDO or CKD. Further expression quantitative trait loci (eQTL) analysis for variants at selected loci showed that rs6550842 and rs35651150 significantly affected the expression of NKIRAS1 and SH2D4A genes in human tissues, respectively. Additionally, we highlighted that the NKIRAS1 and BMP6 genes were correlated with IDO activity and CKD through signaling pathways associated with inflammation. Our data suggest that NKIRAS1, SH2D4A, and BMP6 were potential causative genes affecting IDO activity and CKD through integrated analysis. Identifying these genes could aid in early detection and treatment by predicting the risk of CKD associated with IDO activity.

Hypertension and osteoporosis are two major disorders, which interact with each other. Specific genetic signals involving the fibroblast growth factor receptor-like 1 (FGFRL1) gene are related to high blood pressure and bone growth in giraffes. FGFRL1 is associated with cardiovascular system and bone formation. We performed an association study to investigate the role of FGFRL1 in hypertension, osteoporosis, and height determination in humans. In addition, we identified three kinds of phenotypes in fibroblast growth factor (FGF) genes and examined their association with the FGFRL1 gene. We identified 42 SNPs in the FGFRL1 gene associated with each trait. We then analyzed the potential functional annotation of each SNP. The FGFRL1 gene was found to be associated with height, hypertension, and osteoporosis, consistent with the results of a previous study. In addition, the FGF2, FGF4, FGF10, FGF18, and FGF22 genes were found to interact with the FGFRL1 gene. Our study suggests that both FGFRL1 and FGFRL1-related genes may determine the height and the prevalence of osteoporosis and hypertension in the Korean population.

Osteoporosis is a disease caused by impaired bone remodeling that is especially prevalent in elderly and postmenopausal women. Although numerous chemical agents have been developed to prevent osteoporosis, arguments remain regarding their side effects. Here, we demonstrated the effects of loganin, a single bioactive compound isolated from Cornus officinalis, on osteoblast and osteoclast differentiation in vitro and on ovariectomy (OVX)-induced osteoporosis in mice in vivo. Loganin treatment increased the differentiation of mouse preosteoblast cells into osteoblasts and suppressed osteoclast differentiation in primary monocytes by regulating the mRNA expression levels of differentiation markers. Similar results were obtained in an osteoblast–osteoclast co-culture system, which showed that loganin enhanced alkaline phosphatase (ALP) activity and reduced TRAP activity. In in vivo experiments, the oral administration of loganin prevented the OVX-induced loss of bone mineral density (BMD) and microstructure in mice and improved bone parameters. In addition, loganin significantly increased the serum OPG/RANKL ratio and promoted osteogenic activity during bone remodeling. Our findings suggest that loganin could be used as an alternative treatment to protect against osteoporosis.

Most previous genome-wide association studies (GWAS) have identified genetic variants associated with anthropometric traits. However, most of the evidence were reported in European populations. Anthropometric traits such as height and body fat distribution are significantly affected by gender and genetic factors. Here we performed GWAS involving 64,193 Koreans to identify the genetic factors associated with anthropometric phenotypes including height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip ratio. We found nine novel single-nucleotide polymorphisms (SNPs) and 59 independent genetic signals in genomic regions that were reported previously. Of the 19 SNPs reported previously, eight genetic variants at RP11-513I15.6 and one genetic variant at the RP11-977G19.10 region and six Asian-specific genetic variants were newly found. We compared our findings with those of previous studies in other populations. Five overlapping genetic regions (PAN2, ANKRD52, RNF41, HGMA1, and C6orf106) had been reported previously but none of the SNPs were independently identified in the current study. Seven of the nine newly found novel loci associated with height in women revealed a statistically significant skeletal expression of quantitative trait loci. Our study provides additional insight into the genetic effects of anthropometric phenotypes in East Asians.

Abstract Background Obesity is a serious and common complex disease caused by the influence of genetic and environmental factors. Therefore, we aimed to evaluate the effect of genetic variants on obesity and the possibility of preventing obesity through physical activity using association analysis. Methods This study analyzed the association between obesity and variants in the MACROD2 gene in the Korean association resource (KARE) cohort using logistic regression analysis. Linear regression analysis was performed for obesity‐related phenotype traits including body mass index (BMI), body fat percentage (BFP), abdominal fat percentage (AbFP), and the waist‐to‐hip ratio (WHR). The level of physical activity was analyzed by dividing the participants into two groups according to the cutoff of one hour or more of daily intense activity. Results As a result, rs6079275 in the MACROD2 gene had the highest significance in obesity and phenotypic characteristics. Minor allele carriers (CC, CG) of rs6079275 decreased the obesity risk (OR = 0.57, 95% CI = 0.40–0.82, p = 2.34 × 10−3) and showed a tendency to decrease the risk of BMI (β = −0.312, p = 8.99 × 10−4), BFP (β = −0.482, p = 4.19 × 10−3) and AbFP (β = −0.0051, p = 5.96 × 10−4). In addition, the participants with the minor allele (C) of rs6079275 had a reduced obesity risk with high physical activity (OR = 0.23, 95% CI: 0.14–0.93, p = 0.036). Conclusions This study demonstrated that variants in the MACROD2 gene were correlated with obesity, phenotypic traits, and physical activity in the Korean population. Therefore, we suggest the possibility of preventing obesity by identifying this genetic variation and the interactive effect of lifestyle in Koreans.

Osteoporosis is a common disease caused by an imbalance of processes between bone resorption by osteoclasts and bone formation by osteoblasts in postmenopausal women. The roots of Gentiana lutea L. (GL) are reported to have beneficial effects on various human diseases related to liver functions and gastrointestinal motility, as well as on arthritis. Here, we fractionated and isolated bioactive constituent(s) responsible for anti-osteoporotic effects of GL root extract. A single phytochemical compound, loganic acid, was identified as a candidate osteoprotective agent. Its anti-osteoporotic effects were examined in vitro and in vivo. Treatment with loganic acid significantly increased osteoblastic differentiation in preosteoblast MC3T3-E1 cells by promoting alkaline phosphatase activity and increasing mRNA expression levels of bone metabolic markers such as Alpl, Bglap, and Sp7. However, loganic acid inhibited osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. For in vivo experiments, the effect of loganic acid on ovariectomized (OVX) mice was examined for 12 weeks. Loganic acid prevented OVX-induced bone mineral density loss and improved bone structural properties in osteoporotic model mice. These results suggest that loganic acid may be a potential therapeutic candidate for treatment of osteoporosis.

Bone remodeling is a renewal process regulated by bone synthesis (osteoblasts) and bone destruction (osteoclasts). A previous study demonstrated that Lycii radicis cortex (LRC) extract inhibited ovariectomized (OVX)-induced bone loss in mice. This study investigated the anti-osteoporotic effects of bioactive constituent(s) from the LRC extract. The effective compound(s) were screened, and a single compound, scopolin, which acts as a phytoalexin, was chosen as a candidate component. Scopolin treatment enhanced alkaline phosphatase activity and increased mineralized nodule formation in MC3T3-E1 pre-osteoblastic cells. However, osteoclast differentiation in primary-cultured monocytes was reduced by treatment with scopolin. Consistently, scopolin treatment increased osteoblast differentiation in the co-culture of monocytes (osteoclasts) and MC3T3-E1 (osteoblast) cells. Scopolin treatment prevented bone mineral density loss in OVX-induced osteoporotic mice. These results suggest that scopolin could be a therapeutic bioactive constituent for the treatment and prevention of osteoporosis.

Osteoporosis is a porous bone disease caused by bone density loss, which increases the risk of fractures. Cornus officinalis (CO) and Achyranthes japonica (AJ) have been used as traditional herbal medicine for various disorders in East Asia. Although the anti-osteoporotic effects of single extract of CO and AJ have already been reported, the synergistic effect of a combined mixture has not been studied. In this study, we investigated the effects of a CO and AJ herbal mixture on osteoporosis in in vitro and in vivo models. The results demonstrate that treatment with the CO and AJ mixture significantly promoted osteoblast differentiation of MC3T3-E1 mouse preosteoblasts through the upregulation of osteoblastic differentiation-associated genes such as alkaline phosphatase (Alpl), runt-related transcription factor 2 (Runx2), and bone gamma-carboxyglutamic acid-containing protein (Bglap), while the mixture significantly inhibited differentiation of osteoclasts isolated from primary-cultured mouse monocytes. In addition, oral administration of CO and AJ mixture significantly prevented bone mineral density loss and trabecular bone structures in an ovariectomy-induced osteoporotic mouse model. These results suggest that the combination treatment of CO and AJ mixture might be a beneficial therapy for osteoporosis.

Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) is one of the strongest diabetes loci identified to date; evidence suggests that it plays an important role in insulin secretion. Dietary factors that affect insulin demand might enhance the risk of diabetes associated with CDKAL1 variants. Our aim was to examine the interactions between dietary protein and fat intake and CDKAL1 genetic variants in relation to the risk of diabetes in Korean adults. Single nucleotide polymorphisms (SNPs) were selected with a genome-wide association study (GWAS) for diabetes after adjustment for age, gender, and examination site. Using data from the Health Examinees (HEXA) Study of the Korean Genome and Epidemiology Study (KoGES), 3988 middle-aged Korean adults between 40–76 years of age (2034 men and 1954 women) were included in the study. Finally, rs7756992 located within the CDKAL1 gene region was selected from GWAS (p-value < 5 × 10−8). Multivariable logistic regression models were used to evaluate the interactions between genotypes and dietary protein and fat intake in relation to diabetes risk after adjustment for age, gender, BMI, waist circumference, physical activity, smoking status, drinking habits, and examination site. Significant interactions between CDKAL1 rs7756992 and dietary protein and fat intake for the risk of diabetes were observed in men (p-value < 0.05). In women, significant interactions between dietary protein and fat intake and CDKAL1 variants (rs7756992) were associated with increased risk of diabetes (p-value < 0.05). Dietary protein and fat intake interacted differently with CDKAL1 variants in relation to the risk of diabetes in Korean adults of both genders. These findings indicate that CDKAL1 variants play a significant role in diabetes and that dietary protein and fat intake could affect these associations.

Hypertension is affected by both genetic and dietary factors. This study aimed to examine the interaction between dietary sodium/potassium intake, sodium–potassium ratios, and FGF5 rs16998073 and link these with increased risk for developing hypertension. Using data from the Health Examinee (HEXA) Study of the Korean Genome and Epidemiologic Study (KoGES), we were able to identify a total of 17,736 middle-aged Korean adults who could be included in our genome-wide association study (GWAS) to confirm any associations between hypertension and the FGF5 rs16998073 variant. GWAS analysis revealed that the FGF5 rs16698073 variant demonstrated the strongest association with hypertension in this population. Multivariable logistic regression was used to examine the relationship between dietary intake of sodium, potassium, and sodium–potassium ratios and the FGF5 rs16998073 genotypes (AA, AT, TT) and any increased risk of hypertension. Carriers with at least one minor T allele for FGF5 rs16998073 were shown to be at significantly higher risk for developing hypertension. Male TT carriers with a daily sodium intake ≥2000 mg also demonstrated an increased risk for developing hypertension compared to the male AA carriers with daily sodium intake p-interaction < 0.0001). Female AA carriers with a daily potassium intake ≥3500 mg showed a reduced risk for hypertension when compared to female AA carriers with a daily potassium intake p-interaction < 0.0001). Male TT carriers in the mid-tertile for sodium–potassium ratio values showed the highest odds ratio for hypertension when compared to male AA carriers in the lowest-tertile for sodium–potassium ratio values (AOR = 3.03, 95% CIs = 2.14–4.29, p-interaction < 0.0001). This study confirmed that FGF5 rs16998073 variants do place their carriers (men and women) at increased risk for developing hypertension. In addition, we showed that high daily intake of sodium exerted a synergistic effect for hypertension when combined with FGF5 rs16998073 variants in both genders and that dietary sodium, potassium, and sodium–potassium ratios all interact with FGF5 rs16998073 and alter the risk of developing hypertension in carriers of either gender among Koreans.

Osteoporosis is a common skeletal disease caused by decreased bone mass; it enhances the risk of bone fracture. This study aimed to discover novel herbal extract(s) for the treatment of osteoporosis. We screened 64 ethanol extracts of edible plants native to Korea for their ability to increase the cellular proliferation and differentiation of two osteoblastic cell lines: C3H10T1/2 and MC3T3-E1. We selected a Lycii Radicis Cortex (LRC), Lycium Chinese root bark as the primary candidate. Treatment with LRC extract showed enhanced alkaline phosphatase activity and increased expression of bone metabolic markers Alpl, Runx2, and Bglap genes in both osteoblastic cell lines. There was no effect on the osteoclastic differentiation of primary-cultured monocytes from the mouse bone marrows. Furthermore, the study examined the effect of LRC extract in vivo in ovariectomizd (OVX) mice for 8 weeks and 16 weeks, respectively. Bone mineral density (BMD) was significantly higher in LRC extract-administered group than in the non-LRC-administered OVX control group. The results indicated that LRC extract prevented the OVX-induced BMD loss in mice via promoting the differentiation of osteoblast linage cells. These results suggest that LRC extract may be a good natural herbal medicine candidate for the treatment of osteoporosis.

Congenital cataracts can occur as a non-syndromic isolated ocular disease or as a part of genetic syndromes accompanied by a multi-systemic disease. Approximately 50% of all congenital cataract cases have a heterogeneous genetic basis. Here, we describe three generations of a family with an autosomal dominant inheritance pattern and common complex phenotypes, including bilateral congenital cataracts, short stature, macrocephaly, and minor skeletal anomalies. We did not find any chromosomal aberrations or gene copy number abnormalities using conventional genetic tests; accordingly, we conducted whole-exome sequencing (WES) to identify disease-causing genetic alterations in this family. Based on family WES data, we identified a novel BRD4 missense mutation as a candidate causal variant and performed cell-based experiments by ablation of endogenous BRD4 expression in human lens epithelial cells. The protein expression levels of connexin 43, p62, LC3BII, and p53 differed significantly between control cells and cells in which endogenous BRD4 expression was inhibited. We inferred that a BRD4 missense mutation was the likely disease-causing mutation in this family. Our findings may improve the molecular diagnosis of congenital cataracts and support the use of WES to clarify the genetic basis of complex diseases.

[This corrects the article DOI: 10.1371/journal.pone.0169226.].

Osteoporosis is an abnormal bone remodeling condition characterized by decreased bone density, which leads to high risks of fracture. Previous study has demonstrated that Lycii Radicis Cortex (LRC) extract inhibits bone loss in ovariectomized (OVX) mice by enhancing osteoblast differentiation. A bioactive compound, kukoamine B (KB), was identified from fractionation of an LRC extract as a candidate component responsible for an anti-osteoporotic effect. This study investigated the anti-osteoporotic effects of KB using in vitro and in vivo osteoporosis models. KB treatment significantly increased the osteoblastic differentiation and mineralized nodule formation of osteoblastic MC3T3-E1 cells, while it significantly decreased the osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. The effects of KB on osteoblastic and osteoclastic differentiations under more physiological conditions were also examined. In the co-culture of MC3T3-E1 cells and monocytes, KB promoted osteoblast differentiation but did not affect osteoclast differentiation. In vivo experiments revealed that KB significantly inhibited OVX-induced bone mineral density loss and restored the impaired bone structural properties in osteoporosis model mice. These results suggest that KB may be a potential therapeutic candidate for the treatment of osteoporosis.

Oxidative stress, which results in an excessive product of reactive oxygen species (ROS), is one of the fundamental mechanisms of the development of hypertension. In the vascular system, ROS have physical and pathophysiological roles in vascular remodeling and endothelial dysfunction. In this study, ROS-hypertension-related genes were collected by the biological literature-mining tools, such as SciMiner and gene2pubmed, in order to identify the genes that would cause hypertension through ROS. Further, single nucleotide polymorphisms (SNPs) located within these gene regions were examined statistically for their association with hypertension in 6,419 Korean individuals, and pathway enrichment analysis using the associated genes was performed. The 2,945 SNPs of 237 ROS-hypertension genes were analyzed, and 68 genes were significantly associated with hypertension (p < 0.05). The most significant SNP was rs2889611 within MAPK8 (p = 2.70 × 10-5; odds ratio, 0.82; confidence interval, 0.75 to 0.90). This study demonstrates that a text mining approach combined with association analysis may be useful to identify the candidate genes that cause hypertension through ROS or oxidative stress.

To identify novel susceptibility variants for osteoporosis in Korean postmenopausal women, we performed a genome-wide association analysis of 1180 nonsynonymous single nucleotide polymorphisms (nsSNPs) in 405 individuals with osteoporosis and 722 normal controls of the Korean Association Resource cohort. A logistic regression analysis revealed 72 nsSNPs that showed a significant association with osteoporosis (p

Our previous study showed that ethanol extract of Lycii radicis cortex (LRC) prevented the loss of bone mineral density in ovariectomized mice by promoting the differentiation of osteoblast linage cells. Here, we performed fractionation and isolation of the bioactive compound(s) responsible for the bone formation–enhancing effect of LRC extract. A known sesquiterpene glucoside, (1′R,3′S,5′R,8′S,2Z,4E)-dihydrophaseic acid 3′-O-β-d-glucopyranoside (abbreviated as DPA3G), was isolated from LRC extract and identified as a candidate constituent. We investigated the effects of DPA3G on osteoblast and osteoclast differentiation, which play fundamental roles in bone formation and bone resorption, respectively, during bone remodeling. The DPA3G fraction treatment in mesenchymal stem cell line C3H10T1/2 and preosteoblast cell line MC3T3-E1 significantly enhanced cell proliferation and alkaline phosphatase activity in both cell lines compared to the untreated control cells. Furthermore, DPA3G significantly increased mineralized nodule formation and the mRNA expression of osteoblastogenesis markers, Alpl, Runx2, and Bglap, in MC3T3-E1 cells. The DPA3G treatment, however, did not influence osteoclast differentiation in primary-cultured monocytes of mouse bone marrow. Because osteoblastic and osteoclastic precursor cells coexist in vivo, we tested the DPA3G effects under the co-culture condition of MC3T3-E1 cells and monocytes. Remarkably, DPA3G enhanced not only osteoblast differentiation of MC3T3-El cells but also osteoclast differentiation of monocytes, indicating that DPA3G plays a role in the maintenance of the normal bone remodeling balance. Our results suggest that DPA3G may be a good candidate for the treatment of osteoporosis.