Variations of Wnt/β‐catenin pathway‐related genes in susceptibility to knee osteoarthritis: A three‐centre case‐control study

Huang, Yong; Jiang, Lifeng; Yang, Haoyu; Wu, Lidong; Xu, Nanwei; Zhou, Xindie; Li, Jin

doi:10.1111/jcmm.14696

Cited by 8 publications

(7 citation statements)

References 28 publications

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“…According to Huang et al ( 42 ) the regulation of the Wnt signaling pathway reduced the risk of OA. Charlier et al ( 43 ) reported that the DKK3 regulation of the Wnt/β-catenin pathway increased the dedifferentiation of OA chondrocytes in the human hip and promoted the remission of OA.…”

Section: Discussionmentioning

confidence: 99%

Dickkopf‑3 and β‑catenin play opposite roles in the Wnt/β‑catenin pathway during the abnormal subchondral bone formation of human knee osteoarthritis

et al. 2022

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Osteoarthritis (OA) is condition which poses a main concern to the aging population and its severity is expected to increase with the increasing life expectancy. In the future, several possible targets for OA treatment need to be defined. dickkopf-related protein 3 (dKK3) is an atypical member of the Wnt-antagonistic dickkopf-related protein (dKK) family. The availability of research into the role of dKK3 in the abnormal remodeling of subchondral bone in human knee joints is currently limited. Thus, the aim of the present study was the evaluation of dKK3 expression in the abnormal bone remodeling of subchondral bone in human knee OA in order to clarify the role of dKK3 in subchondral bone remodeling and to acknowledge its potential relevance to β-catenin. In total, 38 specimens were collected from osteotomies of the medial tibial plateau of the human knee. The patient samples were then divided into the normal, mild, moderate and severe symptom groups, according to the Osteoarthritis Research Society International (OARSI) score. Following hematoxylin and eosin (H&E) and Safranin O-fast green staining for alkaline phosphatase (AZO method), changes in the distribution and number of osteocytes in the subchondral bone and the degree of sclerosis of the subchondral bone were observed. Immunohistochemical staining, immunofluorescence, western blot analysis and reverse-transcription quantitative PcR (RT-qPcR) were used for the detection of dKK3 and β-catenin expression level changes in osteoblasts in the subchondral bone of the medial tibial plateau. H&E and alkaline phosphatase staining revealed that the total number of osteocytes in the subchondral bone increased with the severity of the disease. The samples were also evaluated using Safranin O-Fast Green staining and were attributed a score according to the OARSI scoring system: The scoring number and cartilage damage increased along with OA severity. Immunohistochemistry and immunofluorescence assays demonstrated that β-catenin expression in osteocytes increased from mild to moderate, whereas dKK3 expression decreased with the development of arthritis from normal, mild to moderate. According to the results of western blot analysis, β-catenin expression was higher in moderate OA and then decreased in severe OA. On the other hand, the dKK3 levels decreased along with the progression from normal, mild to moderate OA. The results of RT-qPcR demonstrated that β-catenin and dKK3 gene expression differed with the degree of OA. On the whole, the present study demonstrates that dKK3 and β-catenin may play opposite roles in OA subchondral bone remodeling.

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Section: Discussionmentioning

confidence: 99%

Dickkopf‑3 and β‑catenin play opposite roles in the Wnt/β‑catenin pathway during the abnormal subchondral bone formation of human knee osteoarthritis

et al. 2022

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show abstract

Section: Discussionmentioning

confidence: 99%

“…The Wnt pathway is involved in bone and cartilage homeostasis, controls the function of osteoblasts, and affects the differentiation of osteoblasts (Huang et al, 2019; Guo and Cooper, 2007; Li et al, 2019). A genome-wide association study revealed that polymorphisms of Wnt4 were associated with bone mineral densities (Hendrickx et al, 2017), which is consistent with the result of our study.…”

Section: Discussionmentioning

confidence: 99%

Key Promoter Region of Wnt4 response to FSH and Genetic Effect on Several Production Traits of Its Mutations in Chicken

Zhong

Wang

Liu³

et al. 2021

Preprint

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The signaling pathway of the wingless-type mouse mammary tumor virus integration site (Wnt) plays an important role in ovarian and follicular development. Wnt4 was shown in our previous study to be involved in the selection and development of chicken follicles by up-regulating the expression of follicle stimulating hormone receptors (FSHR), stimulating the proliferation of follicular granulosa cells and increasing the secretion of steroidal hormones. To further characterize cis-elements regulating chicken Wnt4 transcription, in this study we determined critical regulatory regions affecting chicken Wnt4 transcription, then identified a single nucleotide polymorphism (SNP) in this region, and finally analyzed the association of the SNP with chicken production traits. The results showed that the 5 regulatory region from -3354 to -2689 of the chicken Wnt4 gene had the strongest activity and greatest response to FSH stimulation, and that one SNP site -3015 (G > C) in this segment was identified as affecting the binding of NFAT5 (nuclear factor of activated T cells 5). When G was replaced by C at this site, it eliminated the binding by NFAT5. Moreover, this locus was significantly associated with the keel length and comb length of hens. Individuals with the genotype CG had longer keels while those with genotype CC had longer combs. Collectively, these data suggested that the SNP-3015 (G > C) is (i) involved in the regulation of Wnt4 gene expression by affecting the binding of NFAT5, (ii) associated with chicken keel length and comb length, and (iii) is a potential DNA marker in the molecular breeding of chickens for egg laying.

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“… 22 However, this SNP was associated with decreased risk of osteoarthritis in women below 60 whose BMI were greater than or equal to 25. 23 …”

Section: Introductionmentioning

confidence: 99%

Associations Between Body Mass Index, WNT16 rs2908004 and Osteoporosis: Findings from Taiwan Biobank

Wu¹,

Nfor²,

Tantoh³

et al. 2022

JMDH

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Purpose Osteoporosis is a degenerative disease that affects women and men of all races. We studied the association between body mass index (BMI), rs2908004 polymorphism of the WNT16 gene, and osteoporosis using data from Taiwan Biobank (TWB). Patients and Methods We analyzed data from 10,942 subjects aged 30 to 70. We defined osteoporosis based on a mean T-score of −2.5 and below in the hip. Body mass index was classified following the guidelines of the Health Promotion Administration. Imputation was carried out using the IMPUTE2 (v2.3.1) program. Multiple logistic regression was used for analysis. The odds ratios (ORs) and 95% confidence interval (CI) for osteoporosis were determined. Results In the multivariate regression model, variant rs2908004 had a significant association with osteoporosis. That is, the rs2908004-GA+AA genotype was associated with lower osteoporosis risk than the GG genotype (OR, 0.651; 95% CI = 0.544 to 0.780). Compared to normal-weight, underweight was significantly associated with a higher risk of osteoporosis (OR, 6.517; 95% CI = 4.624 to 9.186) while overweight and obesity were protective (OR, 0.176; 95% CI = 0.140 to 0.221 and 0.057; 95% CI = 0.039 to 0.083, respectively). There was an interaction between rs2908004 and BMI ( p = 0.0148). Subgroup analyses (using rs2908004-GG/normal-weight as the reference group) indicated ORs of 7.66 (95% CI = 5.153 to 11.394) in the rs2908004-GG/underweight group and 3.002 (95% CI = 1.509 to 5.974) in the rs2908004-GA+AA/underweight group (95% CI = 1.509 to 5.974). Odds ratios were substantially lower in rs2908004-GG/obese, rs2908004-GG/overweight, GA+AA/normal-weight, rs2908004-GA+AA/overweight, and rs2908004-GA+AA/obese groups, respectively. Conclusion According to our study, underweight was associated with an increased risk of osteoporosis irrespective of WNT16 rs2908004 genotypes, while overweight and obesity were associated with a lower risk.

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Variations of Wnt/β‐catenin pathway‐related genes in susceptibility to knee osteoarthritis: A three‐centre case‐control study

Cited by 8 publications

References 28 publications

Dickkopf‑3 and β‑catenin play opposite roles in the Wnt/β‑catenin pathway during the abnormal subchondral bone formation of human knee osteoarthritis

Dickkopf‑3 and β‑catenin play opposite roles in the Wnt/β‑catenin pathway during the abnormal subchondral bone formation of human knee osteoarthritis

Key Promoter Region of Wnt4 response to FSH and Genetic Effect on Several Production Traits of Its Mutations in Chicken

Associations Between Body Mass Index, WNT16 rs2908004 and Osteoporosis: Findings from Taiwan Biobank

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