Upregulated Cellular Expression of IL-17 by CD4+ T-Cells in Osteoporotic Postmenopausal Women

Abstract

Aim: The study aimed to investigate cellular expression of IL-17 by CD4+ T-cells in osteoporotic postmenopausal women. Methods: We enrolled 25 postmenopausal women with osteoporosis (PostMO) and 25 postmenopausal women with normal bone mineral density measurements (PostM) to examine the production of IL-17, tumor necrosis factor a (TNFa) and receptor activator of nuclear factor γ-B ligand (RANKL) by CD4+ T-cells and IL-17, RORγt, TNFa and RANKL mRNA levels in CD4+ T-cells. Circulating concentrations of IL-17 along with IL-6, TNFa, RANKL and osteoprotegerin (OPG) were also determined. Results: Osteoporotic postmenopausal women had higher serum concentrations of IL-17 (3.7 ± 1.3 vs. 2.5 ± 1.1 ng/ml, p = 0.042), IL-6 (158 ± 56 vs. 105 ± 39 pg/ml, p = 0.044), TNFa (138 ± 41 vs. 74 ± 11 pg/ml, p < 0.001) and OPG (1.7 ± 0.4 vs. 1.3 ± 0.4 ng/ml, p = 0.039) than healthy controls. The IL-17-producing CD4+ T-cells were higher in the PostMO group than in the PostM group (7.1 ± 2.4 vs. 4.9 ± 1.4%, p = 0.0015). Additionally, osteoporotic postmenopausal women had greater mRNA levels of IL-17 (3.5 ± 2.9 vs. 1.2 ± 1.0%, p = 0.019) and RORγt (5.7 ± 2.5 vs. 2.2 ± 1.0%, p < 0.001) in CD4+ T-cells than in healthy controls. Conclusions: Our findings implied that the upregulated production of IL-17 may play an important role in regulating bone loss in osteoporotic postmenopausal women.

Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice

“…Although aspects of these findings such as the increase in IL‐7, IL‐15, and IL‐17A have been noted to increase post‐OVX in mice and in postmenopausal women with osteoporosis, our study connects the cellular and signaling components into a coherent description. The role of DCs and FasL have also been previously noted .…”

“…Pioneering studies by Roggia and colleagues showed that in mice, ovariectomy (OVX) leads to increased TNFα‐producing T cells in the bone marrow. Furthermore, whereas postmenopausal women with normal bone density have undetectable levels of IL‐17A, postmenopausal osteoporotic women have detectable levels of IL‐17A in peripheral blood . Together, these results suggest that low‐grade inflammation promotes or is associated with bone loss in some postmenopausal women.…”

Pulsed low-dose RANKL as a potential therapeutic for postmenopausal osteoporosis

“…These T EFF are detected in the BM at earlier time points but could be detected in peripheral blood at 90 days in untreated mice (Figure 3). These T cells producing TNFα, IL-6, and IL-17A have been observed in postmenopausal osteoporotic women (47) and may contribute to other comorbidities such as mood disorders, joint pain, and atherosclerosis observed in postmenopausal women.…”

Role of odanacatib in reducing bone loss due to endodontic disease: An overview

“…TNF-α leads to cell migration towards the infected and inflamed site, inducing the upregulation of adhesion molecules and production of chemotactic chemokines. [ 4 5 ] It plays a central role in inflammatory reaction, bone resorption, and loss of connective tissue. It further upregulates the production of other proinflammatory innate immune cytokines such as IL-1β and IL-6.…”

“…It further upregulates the production of other proinflammatory innate immune cytokines such as IL-1β and IL-6. [ 4 5 6 ] The latter are involved in inflammatory cell migration and osteoclastogenic process. [ 6 7 ] Absence of innate immunity cytokines attenuates inflammatory bone loss but their simultaneous inhibition results in more effective protection leading to almost complete remission of bone loss.…”