Jiesheng Rong

Body mass index and susceptibility to knee osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE Excess bodyweight, expressed as increased body mass index, is associated with osteoarthritis risk, especially in weight bearing joints. However, the strength of the association was inconsistent. The study was conducted to quantitatively assess the association between body mass index and the risk of knee osteoarthritis and investigate the difference of the strength stratified by sex, study type and osteoarthritis definition. METHODS We used published guidelines of the Meta-analysis of Observational Studies in Epidemiology Group (MOOSE) to perform the meta-analysis. The search strategy employed included computerized bibliographic searches of MEDLINE, PubMed, EMBASE, The Cochran Library and references of published manuscripts. Study-specific incremental estimates were standardized to determine the risk of knee osteoarthritis associated with a 5 kg/m(2) increase in BMI. RESULTS Twenty-one studies were included in the study. The results showed that body mass index was significantly positive associated with osteoarthritis risk in knee site. A 5-unit increase in body mass index was associated with an 35% increased risk of knee osteoarthritis (RR: 1.35; 95%CI: 1.21, 1.51). Magnitude of the association was significantly stronger in women than that in men with significant difference (men, RR: 1.22; 95%CI: 1.19, 1.25; women, RR: 1.38; 95%CI: 1.23, 1.54; p=0.04). The summary effect size was 1.25(95%CI: 1.18, 1.32) in case-control studies and 1.37 (95%CI: 1.19, 1.56) in cohort studies (p=0.28). Body mass index was positively associated with knee osteoarthritis defined by radiography and/or clinical symptom (RR: 1.25, 95%CI: 1.17, 1.35) and clinical surgery (RR: 1.54, 95%CI: 1.29, 1.83). The latter tended to be stronger than the former (p<0.01). CONCLUSION Increased body mass index contribute to a substantially increased risk of knee OA. The magnitude of the association varies by sex and OA definition.

The relationship between body mass index and hip osteoarthritis: A systematic review and meta-analysis

OBJECTIVE Body mass index, a measure of relative weight, is increasingly recognized as an important risk factor for osteoarthritis, especially in weight bearing joints. The objective was to assess the association between body mass index and hip osteoarthritis susceptibility and investigate the difference between sex, study type and osteoarthritis definition. METHODS We did electronic searches of Medline, Embase and Cochrane library from the commencement to December 2009. A meta-analysis and meta-regression was executed to quantitatively assess the strength of associations between body mass index and hip osteoarthritis risk. Study-specific incremental estimates were standardized to determine the risk associated with a 5 kg/m(2) increase in body mass index. RESULTS Fourteen epidemiological studies were included. Our study showed that body mass index was significantly positive associated with hip osteoarthritis risk. A 5-unit increase in body mass index was related to an increased risk of hip osteoarthritis (RR: 1.11; 95%CI: 1.07, 1.16). The magnitudes of associations were similar in women as compared with men (women, RR: 1.10; 95%CI: 1.05, 1.15; men, RR: 1.08; 95%CI: 1.04, 1.12; p > 0.05). The summary estimates were 1.12 (95%CI: 1.02, 1.24) in case-control studies and 1.11 (95%CI: 1.06, 1.16) in cohort studies (p > 0.05). Body mass index was positively associated with hip osteoarthritis defined by radiography and/or clinical symptom (RR: 1.04; 95%CI: 1.00, 1.07) and clinical surgery (RR: 1.16; 95%CI: 1.11, 1.22) with no significant difference (p > 0.05). CONCLUSION Increased body mass index contributes to a positive effect on susceptibility to hip osteoarthritis. Associations between body mass index and hip osteoarthritis risk do not vary by sex, study design or osteoarthritis definition.

MATN3 Gene Polymorphism Is Associated with Osteoarthritis in Chinese Han Population: A Community-Based Case-Control Study

Background. The matrilin, especially matrilin-3 (MATN3), are reported to play important roles in the pathophysiology of osteoarthritis (OA). To explore the relationship between MATN3 SNP6 (rs8176070) and primary OA, we conducted a community-based case-control study. Methods. A total of 732 community residents aged 40–84 years participated in the community-based study in Northeast China. After taking physical and radiographic examinations, 420 of the residents were diagnosed OA (216 women and 204 men). The other 312 individuals without any symptoms of osteoarthritis or signs in the radiographs (156 women and 156 men) were considered as healthy controls. After obtaining the DNA of case and control groups, genotypes of the MATN3 SNP6 were determined by polymerase chain reaction followed by restriction enzyme digestion. The numbers of patients with different OA subtypes were also calculated. Results. The distribution of genotypes and alleles of the MATN3 SNP6 between OA patients and controls was different significantly. The BB carrier tends to be associated with the increased osteoarthritis (P = 0.025, OR = 1.724, 95% CI = 1.071–2.77), especially the knee osteoarthritis (P = 0.021, OR = 2.402, 95% CI = 1.141–5.060) and lumber osteoarthritis (P = 0.020, OR = 1.880, 95% CI = 1.103–3.204). Bb carrier increased hand osteoarthritis risk (P = 0.002, OR = 5.380, 95% CI = 1.828–15.835). The B allele might have an effect on the increased knee osteoarthritis (P = 0.000, OR = 3.143, 95% CI = 2.283–4.328). Conclusion. These findings suggest that the MATN3 gene polymorphism might be associated with osteoarthritis in the Chinese Han population.

Decreased proliferation ability and differentiation potential of mesenchymal stem cells of osteoporosis rat

OBJECTIVE To explore decreased proliferation ability and differentiation potential of mesenchymal stem cells (MSCs) of osteoporosis rat. METHODS MSCs were obtained from osteoporosis rat, and proliferation potency and impaired osteogenic differentiation potential were determined. RESULTS The result showed a significant downregulation of MSCs pluripotency related gene (Oct 4) and osteogenic genes (BSP, OCN) expression in OVX MSCs compared with Sham MSCs (P<0.05). CONCLUSIONS These data suggest that MSCs are aging in osteoporosis body, and autologous OVX MSCs transplantation is not appropriate to treat osteoporosis if necessary. There will be a possibility in establishing a new clinical application of MSCs autologous transplantation to treat osteoporosis, if OVX MSCs have stronger proliferation and differentiation.

Strong association of the polymorphisms in PBEF1 and knee OA risk: a two-stage population-based study in China

The association of Pre-B cell colony enhancing factor 1 (PBEF1) with obesity, together with its pro-inflammatory properties suggests that PBEF1 might be another crucial mediator that links inflammation with obesity and primary osteoarthritis (OA). We hypothesized that polymorphisms in PBEF1 may modify the risk of developing OA. Thus we systematically screened 4 tagging polymorphisms (rs4730153, rs2058540, rs3801267 and rs16872158) in PBEF1 and evaluated the association between the genetic variants and OA risk in a two-stage case-control study including 196 cases and 442 controls in the first stage and 143 cases and 238 controls in the second stage. In the first stage, two SNPs (rs4730153 and rs16872158) were found to be potentially associated with OA risk (P < 0.05), which were further confirmed in the second stage with similar effects. After combining the two stages, we found that rs4730153 was significantly associated with decreased risk of OA in an additive genetic model (P < 0.05), while rs16872158 showed increased risk of developing OA (P < 0.05). Combined analysis of these 2 SNPs showed a significant allele-dosage association between the number of risk alleles and OA risk (Ptrend = 5.25 × 10−5). These findings indicate that genetic variants in PBEF1 gene may modify individual susceptibility to OA in the Chinese population.

No association of the single nucleotide polymorphism rs8044769 in the fat mass and obesity-associated gene with knee osteoarthritis risk and body mass index: A population-based study in China

Objectives Previous genome-wide association studies (GWAS) have reported significant association of the single nucleotide polymorphism (SNP) rs8044769 in the fat mass and obesity-associated gene (FTO) with osteoarthritis (OA) risk in European populations. However, these findings have not been confirmed in Chinese populations. Methods We systematically genotyped rs8044769 and evaluated the association between the genetic variants and OA risk in a case-controlled study including 196 OA cases and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Results We found that the variant T allele of rs8044769 showed no significant association of OA risk (p = 0.791), or association with body mass index (BMI) (pmeta = 0.786) in an additive genetic model. However, we detected a significant interaction between rs8044769 genotypes and BMI on OA risk (p = 0.037), as well as a borderline interaction between rs8044769 genotypes and age on OA risk (p = 0.062). Conclusions Our findings indicate that rs8044769 in the FTO gene may not modify individual susceptibility to OA or increased BMI in the Chinese population. Further studies are warranted to validate and extend our findings. Cite this article: Prof L. Jiang. No association of the single nucleotide polymorphism rs8044769 in the fat mass and obesity-associated gene with knee osteoarthritis risk and body mass index: A population-based study in China. Bone Joint Res 2016;5:169–174. DOI: 10.1302/2046-3758.55.2000589.

Multiple gene-specific DNA methylation in blood leukocytes and colorectal cancer risk: a case-control study in China

The relationship between gene-specific DNA methylation in peripheral blood leukocytes and colorectal cancer (CRC) susceptibility is unclear. In this case-control study, the methylation status of a panel of 10 CRC-related genes in 428 CRC cases and 428 cancer-free controls were detected with methylation-sensitive high-resolution melting analysis. We calculated a weighted methylation risk score (MRS) that comprehensively combined the methylation status of the panel of 10 genes and found that the MRS_10 was significantly associated with CRC risk. Compared with MRS-Low group, MRS-High group and MRS-Medium group exhibited a 6.51-fold (95% CI, 3.77-11.27) and 3.85-fold (95% CI, 2.72-5.45) increased risk of CRC, respectively. Moreover, the CRC risk increased with increasing MRS_10 (Ptrend < 0.0001). Stratified analyses demonstrated that the significant association retained in both men and women, younger and older, and normal weight or underweight and overweight or obese subjects. The area under the receiver operating characteristic curves for the MRS_10 model was 69.04% (95% CI, 65.57-72.66%) and the combined EF and MRS_10 model yielded an AUC of 79.12% (95% CI, 76.22-82.15%). Together, the panel of 10 gene-specific DNA methylation in leukocytes was strongly associated with the risk of CRC and might be a useful marker of susceptibility for CRC.The relationship between gene-specific DNA methylation in peripheral blood leukocytes and colorectal cancer (CRC) susceptibility is unclear. In this case-control study, the methylation status of a panel of 10 CRC-related genes in 428 CRC cases and 428 cancer-free controls were detected with methylation-sensitive high-resolution melting analysis. We calculated a weighted methylation risk score (MRS) that comprehensively combined the methylation status of the panel of 10 genes and found that the MRS_10 was significantly associated with CRC risk. Compared with MRS-Low group, MRS-High group and MRS-Medium group exhibited a 6.51-fold (95% CI, 3.77-11.27) and 3.85-fold (95% CI, 2.72-5.45) increased risk of CRC, respectively. Moreover, the CRC risk increased with increasing MRS_10 (Ptrend < 0.0001). Stratified analyses demonstrated that the significant association retained in both men and women, younger and older, and normal weight or underweight and overweight or obese subjects. The area under the receiver operating characteristic curves for the MRS_10 model was 69.04% (95% CI, 65.57-72.66%) and the combined EF and MRS_10 model yielded an AUC of 79.12% (95% CI, 76.22-82.15%). Together, the panel of 10 gene-specific DNA methylation in leukocytes was strongly associated with the risk of CRC and might be a useful marker of susceptibility for CRC.

Variations in the PBEF1 gene are associated with body mass index: A population-based study in northern China

Objective PBEF1 and its polymorphisms may be important in the physiopathology of obesity. We hypothesized that polymorphisms in PBEF1 gene may modify body mass index (BMI). Methods Thus, we systematically screened 4 tagging polymorphisms (rs4730153, rs2058540, rs3801267 and rs16872158) in PBEF1 gene and evaluated the association between the genetic variants and BMI in a population-based study including 442 subjects in northern China. Results We found that the SNP rs3801267 was significantly associated with decreased BMI (P = 0.026 in additive model), while the other 2 SNPs (rs4730153 and rs16872158) showed a borderline significant association with decreased BMI (P = 0.068 and 0.060 in additive models). Combined analysis of these 3 SNPs showed a significant allele–dosage association between the number of variant alleles and decreased BMI (Ptrend = 0.007). Conclusions These findings indicate that genetic variants in PBEF1 gene may modify individual BMI in the Chinese population.