Association of circulating dipeptidyl-peptidase 4 levels with osteoporotic fracture in postmenopausal women

Kim, H.; Baek, Ki Hyun; Lee, S.-Y.; Ahn, Seong Hee; Lee, S. H.; Koh, Jung‐Min; Rhee, Yumie; Kim, C. H.; Kim, D.-Y.; Kang, Moo Il; Kim, B.-J.; Min, Yong Ki

doi:10.1007/s00198-016-3839-5

Cited by 13 publications

(11 citation statements)

References 40 publications

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“…Of these secreted factors, bone marrow concentrations of DPP4 and CST3 were found to be decreased in bone marrow plasma of DMAb-treated women (p = 0.056 and p < 0.05, respectively; Kruskal-Wallis), and serum DPP4 levels were significantly reduced following treatment with DMAb. Moreover, the bone marrow (and peripheral blood) concentrations of DPP4 correlated significantly with both osteoclast and osteoblast gene sets in placebo patients, consistent with previous reports that DPP4 correlates with increased bone remodeling in postmenopusal women 24,25 .…”

Section: Discussionsupporting

confidence: 90%

“…Thus, DPP4 inhibitors, such as sitagliptin, increase GLP-1 levels, leading to increased insulin synthesis and secretion, decreased glucagon release, and decreased plasma glucose. DPP4 has previously been shown to be increased in postmenopausal women and correlates with increased rates of bone turnover 24,25 . Since our mRNA expression analysis revealed DPP4 as an osteoclast-derived factor, we used in situ hybridization to assess for localization of DPP4 mRNA expression in bone.…”

Section: Resultsmentioning

confidence: 96%

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Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism

et al. 2020

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Bone remodeling consists of resorption by osteoclasts followed by formation by osteoblasts, and osteoclasts are a source of bone formation-stimulating factors. Here we utilize osteoclast ablation by denosumab (DMAb) and RNA-sequencing of bone biopsies from postmenopausal women to identify osteoclast-secreted factors suppressed by DMAb. Based on these analyses, LIF, CREG2, CST3, CCBE1, and DPP4 are likely osteoclast-derived coupling factors in humans. Given the role of Dipeptidyl Peptidase-4 (DPP4) in glucose homeostasis, we further demonstrate that DMAb-treated participants have a significant reduction in circulating DPP4 and increase in Glucagon-like peptide (GLP)-1 levels as compared to the placebo-treated group, and also that type 2 diabetic patients treated with DMAb show significant reductions in HbA1c as compared to patients treated either with bisphosphonates or calcium and vitamin D. Thus, our results identify several coupling factors in humans and uncover osteoclast-derived DPP4 as a potential link between bone remodeling and energy metabolism.

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 96%

Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism

et al. 2020

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“…3d in File S1). Finally, we measured the expression of Dpp4 , another member of the dipeptidyl peptidase family recently implicated in bone metabolism, and we did not find significant changes either in total bone or in in vitro differentiated OCs (Supporting Fig. 3e in File S1).…”

Section: Resultsmentioning

confidence: 89%

Absence of Dipeptidyl Peptidase 3 Increases Oxidative Stress and Causes Bone Loss

Menale

Robinson

Palagano

et al. 2019

Journal of Bone and Mineral Research

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Controlling oxidative stress through the activation of antioxidant pathways is crucial in bone homeostasis, and impairments of the cellular defense systems involved contribute to the pathogenesis of common skeletal diseases. In this work we focused on the dipeptidyl peptidase 3 (DPP3), a poorly investigated ubiquitous zinc‐dependent exopeptidase activating the Keap1‐Nrf2 antioxidant pathway. We showed Dpp3 expression in bone and, to understand its role in this compartment, we generated a Dpp3 knockout (KO) mouse model and specifically investigated the skeletal phenotype. Adult Dpp3 KO mice showed a mild growth defect, a significant increase in bone marrow cellularity, and bone loss mainly caused by increased osteoclast activity. Overall, in the mouse model, lack of DPP3 resulted in sustained oxidative stress and in alterations of bone microenvironment favoring the osteoclast compared to the osteoblast lineage. Accordingly, in vitro studies revealed that Dpp3 KO osteoclasts had an inherent increased resorptive activity and ROS production, which on the other hand made them prone to apoptosis. Moreover, absence of DPP3 augmented bone loss after estrogen withdrawal in female mice, further supporting its relevance in the framework of bone pathophysiology. Overall, we show a nonredundant role for DPP3 in the maintenance of bone homeostasis and propose that DPP3 might represent a possible new osteoimmunological player and a marker of human bone loss pathology. © 2019 American Society for Bone and Mineral Research.

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“…Kim et al . recently observed an association between DPP4 activity levels and osteoporotic fracture risk in non-diabetic postmenopausal women, finding that high levels were associated with elevated BR markers; the authors indicated that bone formation and resorption was influenced by certain DPP4 substrates 25 . Zheng et al .…”

Section: Discussionmentioning

confidence: 99%

“…Although a relationship has been demonstrated between DPP4 and osteoporosis in non-diabetic postmenopausal women 25,26 there is little evidence on the association of GLP1 with osteoporosis in humans with no glucose metabolism disorder. Confirmation of this relationship would be of interest, especially in relation to GLP1, because drugs based on these peptides are used in diabetes mellitus and may be of potential value in the treatment of osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

Glucagon-like peptide 1 and Glucagon-like peptide 2 in relation to osteoporosis in non-diabetic postmenopausal women

Castillo

Martínez-Ramírez

Arroyo

et al. 2019

Sci Rep

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Osteoporosis results from an imbalance in bone remodeling, which is known to follow a circadian rhythm determined by a functional relationship between intestine and bone tissue. Specific intestinal peptides have been identified as mediators. Glucagon-like peptide 1 and glucagon-like peptide 2, have been associated with bone health. Our main objective was to determine whether postprandial plasma levels of glucagon-like peptide 1, glucagon-like peptide 2 and dipeptidyl-peptidase 4 activity, are associated with osteoporosis in non-diabetic postmenopausal women. We studied non-diabetic postmenopausal women with osteoporosis diagnosed by dual-energy X-ray absorptiometry (cases, n = 43) and age-matched (±1 yr) controls without osteoporosis or a history of osteoporotic fracture (n = 43). We measured postprandial plasma levels of glucagon-like peptide 1, glucagon-like peptide 2, and dipeptidyl-peptidase 4 activity, bone mineral density, and baseline levels of bone remodeling markers and analyzed the food intake using a food-frequency questionnaire. Postprandial glucagon-like peptide 1 values were lower (p < 0.001) in cases, μ (SEM) = 116.25 (2.68), than in controls, μ (SEM) = 126.79 (2.68). Glucagon-like peptide 1 was associated with reduced osteoporosis risk in the crude logistic regression analysis [OR (95% CI) = 0.724 (0.53–0.97), p = 0.031] and adjusted analysis [OR = 0.603 (0.38–0.94), p = 0.027]. We found no association of glucagon-like peptide 2, or dipeptidyl-peptidase 4 activity with osteoporosis. Postprandial glucagon-like peptide 1 levels are related to osteoporosis and osteoporosis risk in non-diabetic postmenopausal women. Further studies are required to verify these findings.

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Association of circulating dipeptidyl-peptidase 4 levels with osteoporotic fracture in postmenopausal women

Abstract: DPP4 may be associated with OF by at least partly mediating the bone turnover rate. Circulating DPP4 levels may be a potential biomarker that could increase the predictive power of current fracture risk assessment models.

Cited by 13 publications

References 40 publications

Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism

Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism

Absence of Dipeptidyl Peptidase 3 Increases Oxidative Stress and Causes Bone Loss

Glucagon-like peptide 1 and Glucagon-like peptide 2 in relation to osteoporosis in non-diabetic postmenopausal women

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