CTRP3 is Significantly Decreased in Patients with Primary Hyperparathyroidism and Closely Related with Osteoporosis

Demirtaş, Derya; Acibucu, Fettah; Baylan, Filiz Alkan; Gulumsek, Erdinc; Saler, Tayyibe

doi:10.1055/a-0899-5210

Cited by 6 publications

(7 citation statements)

References 23 publications

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“…C1qtnf3 encodes complement C1q/tumour necrosis factor-related protein 3 (CTRP3), which is generally described as an adipokine because it exerts systemic effects, including anti-inflammatory effects and regulation of glucose metabolism ( Li et al, 2018 ). Clinically, it has recently been shown that low serum CTRP3 levels are associated with osteoporosis ( Demirtas et al, 2020 ), an observation in keeping with a putative role for this factor as a mediator of PAR 2 's pro-osteogenic and anti-adipogenic effects. G protein-coupled receptor 35, encoded by Gpr35 , was until recently considered to be an orphan G protein-coupled receptor ( Milligan, 2018 ).…”

Section: Discussionmentioning

confidence: 73%

Protease-activated receptor-2 promotes osteogenesis in skeletal mesenchymal stem cells at the expense of adipogenesis: Involvement of interleukin-6

et al. 2021

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Bone marrow mesenchymal stem cells (MSCs) give rise to osteoblasts and adipocytes, with an inverse relationship between the two. The MSCs from protease-activated receptor-2 knockout (PAR 2 KO) mice have a reduced capacity to generate osteoblasts. Here we describe the observation that PAR 2 KO osteoblastic cultures generate more adipocytes than wildtype (WT) cultures. Osteoblasts from PAR 2 KO mice expressed lower levels of osteoblastic genes ( Runx2 , Col1a1 and Bglap ), and higher levels of the adipocytic gene Pparg than WT osteoblasts. Bone marrow stromal cells from PAR 2 KO mice generated fewer osteoblastic colonies (assessed by staining for alkaline phosphatase activity and mineral deposition) and more adipocytic (Oil Red-O positive) colonies than cultures from WT mice. Similarly, cultures of the bone marrow stromal cell line (Kusa 4b10) in which PAR 2 was knocked down ( F2rl1 KD), were less osteoblastic and more adipocytic than vector control cells. Putative regulators of PAR 2 -mediated osteogenesis and suppression of adipogenesis were identified in an RNA-sequencing (RNA-seq) investigation; these include C1qtnf3 , Gpr35 , Grem1 , Snorc and Tcea3 , which were more highly expressed, and Cnr1 , Enpep , Hmgn5 , Il6 and Ramp3 which were expressed at lower levels, in control than in F2rl1 KD cells. Interleukin-6 (IL-6) levels were higher in medium harvested from F2rl1 KD cells than from control cells, and a neutralising anti-IL-6 antibody reduced the number of adipocytes in F2rl1 KD cultures to that of control cultures. Thus, PAR 2 appears to be a mediator of the reciprocal relationship between osteogenesis and adipogenesis, with IL-6 having a regulatory role in these PAR 2 -mediated effects.

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Section: Discussionmentioning

confidence: 73%

Protease-activated receptor-2 promotes osteogenesis in skeletal mesenchymal stem cells at the expense of adipogenesis: Involvement of interleukin-6

et al. 2021

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“…For example, in a study by Demirtas et al. (2020), CTRP3 levels decreased significantly decreased in patients with PHPT, and they were also related to osteoporosis, which is a surgical criterion in PHPT 19 . Also, in a study conducted by Gulumsek et al (2022), native SH (thiol) values were lower in PHPT patients who were candidates for surgery.…”

Section: Discussionmentioning

confidence: 98%

Serum Periostin Levels are Significantly Higher in Patients with Primary Hyperparathyroidism and Closely Related to Osteoporosis

Yigitdol,

Gulumsek,

Ozturk

et al. 2023

Exp Clin Endocrinol Diabetes

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Background Periostin is an emerging biomarker that plays a role in bone metabolism and may be associated with bone mineral density (BMD). This study is aimed to investigate serum periostin levels in patients with primary hyperparathyroidism (PHPT) and its correlation with BMD in these patients. Methods Forty patients with newly diagnosed PHPT without co-morbidities and 30 healthy controls were included. Laboratory tests for the diagnosis of PHPT and serum levels of periostin were measured for all patients. BMD was measured on lumbar spines L1 and L4 by dual-energy X-ray absorptiometry (DEXA). Serum periostin levels were detected using an enzyme-linked immunosorbent assay (ELISA). Results Serum periostin levels were significantly higher in patients with PHPT than in healthy controls (p<0.001). Serum periostin levels were also significantly higher (mean 59.7±11.0 ng/mL) in PHPT patients with osteoporosis than those without osteoporosis (p=0.004). In logistic regression analysis, only serum periostin levels independently predicted the patients with osteoporosis. According to this analysis, every 1 ng/mL increase in serum periostin increased the risk of having osteoporosis by 20.6%. When the cut-off for serum periostin level was 49.75 ng/mL, the patients with osteoporosis were predicted with 71.4% sensitivity and 69.2% specificity. Multivariate regression analysis revealed a negative correlation between serum periostin levels and L1-L4 T scores on DEXA. Conclusion This is the first study to determine that serum periostin levels are higher in PHPT patients than those without PHPT and to demonstrate a significant association between serum periostin levels and T scores on DEXA in patients with PHPT. These findings will aid in detecting osteoporosis in patients with PHPT and making the decision for surgery in PHPT patients with no need for DEXA imaging that involves radiation.

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“…Serum CTRP3 levels have been shown to be decreased in patients with osteoporosis, and a significant decrease in the incidence of osteoporosis has been observed in the presence of CTRP3 (6). The results of a previous study demonstrated that the serum levels of CTRP3 in patients with primary hyperparathyroidism are lower than those observed in healthy controls (7). In addition, the serum levels of CTRP3 in patients with primary hyperparathyroidism with osteoporosis were shown to be lower than those in patients with primary hyperparathyroidism without osteoporosis.…”

Section: Introductionmentioning

confidence: 96%

“…In addition, the serum levels of CTRP3 in patients with primary hyperparathyroidism with osteoporosis were shown to be lower than those in patients with primary hyperparathyroidism without osteoporosis. The results of a logistic regression analysis further revealed that CTRP3 levels may be used to independently determine whether a patient has osteoporosis (7). However, the specific role of CTRP3 in osteoporosis has yet to be fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

gCTRP3 inhibits oophorectomy‑induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway in mice

Zhang,

Zhao

et al. 2024

Mol Med Rep

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C1q/tumor necrosis factor-related protein 3 (CTRP3) expression is markedly reduced in the serum of patients with osteoporosis. The present study aimed to investigate whether CTRP3 reduces bone loss in oophorectomy (OVX)-induced mice via the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/nuclear factor E2-related factor 2 (Nrf2) signaling pathway. Female C57BL/6J mice and MC3T3-E1 cells were used to construct in vivo and in vitro models of osteoporosis, respectively. The left femurs of mice were examined using micro-computed tomography scans and bone-related quantitative morphological evaluation was performed. Pathological changes and the number of osteoclasts in the left femurs of mice were detected using hematoxylin and eosin, and tartrate-resistant acid phosphatase (TRAP) staining. Runt-related transcription factor-2 (RUNX2) expression in the left femurs was detected using immunofluorescence analysis, and the serum levels of bone resorption markers (C-telopeptide of type I collagen and TRAP) and bone formation markers [osteocalcin (OCN) and procollagen type 1 N-terminal propeptide] were detected. In addition, osteoblast differentiation and calcium deposits were examined in MC3T3-E1 cells using alkaline phosphatase (ALP) and Alizarin red staining, respectively. Moreover, RUNX2, ALP and OCN expression levels were detected using reverse transcription-quantitative PCR, and the expression levels of proteins associated with the AMPK/SIRT1/Nrf2 signaling pathway were detected using western blot analysis. The results revealed that globular CTRP3 (gCTRP3) alleviated bone loss and promoted bone formation in OVX-induced mice. gCTRP3 also facilitated the osteogenic differentiation of MC3T3-E1 cells through the AMPK/SIRT1/Nrf2 signaling pathway. The addition of an AMPK inhibitor (Compound C), SIRT1 inhibitor (EX527) or Nrf2 inhibitor (ML385) reduced the osteogenic differentiation of MC3T3-E1 cells via inhibition of gCTRP3. In conclusion, gCTRP3 inhibits OVX-induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway.

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CTRP3 is Significantly Decreased in Patients with Primary Hyperparathyroidism and Closely Related with Osteoporosis

Cited by 6 publications

References 23 publications

Protease-activated receptor-2 promotes osteogenesis in skeletal mesenchymal stem cells at the expense of adipogenesis: Involvement of interleukin-6

Protease-activated receptor-2 promotes osteogenesis in skeletal mesenchymal stem cells at the expense of adipogenesis: Involvement of interleukin-6

Serum Periostin Levels are Significantly Higher in Patients with Primary Hyperparathyroidism and Closely Related to Osteoporosis

gCTRP3 inhibits oophorectomy‑induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway in mice

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