Implication of IL-17 in Bone Loss and Structural Damage in Inflammatory Rheumatic Diseases

Abstract

Proinflammatory cytokines play an important role in the systemic and focal bone loss associated with chronic inflammatory diseases. Targeting these cytokines with biologics and small molecules has led to a major improvement of the bone health of patients with inflammatory arthritis. Cytokines from the IL-17 family have been shown to be involved in the pathogenesis of several diseases such as spondyloarthritis, psoriatic arthritis, or psoriasis. IL-17A has been the first described and the most studied. The recent development of targeted therapies against IL-17A or its receptor and their efficacy has confirmed the importance of this cytokine in the development of inflammatory diseases. The aim of this review was to describe the effects of the IL-17 family and more particularly of IL-17A on bone and cartilage tissues. At the cellular level, IL-17A is proosteoclastogenic whereas its effects on osteoblasts depend on the stage of differentiation of these cells. In vivo, IL-17A is not required for normal bone homeostasis but plays an important role in bone loss notably in an ovariectomized mouse model of osteoporosis. Preliminary data from clinical trials showed a stabilisation of bone density in patients treated with anti-IL-17A antibodies. IL-17A plays a central role in the cartilage damage through the induction of collagenases and by decreasing the expression of their inhibitors in synergy with the other proinflammatory cytokines. The prevention of structural damage by anti-IL-17A therapies has been demonstrated in several pivotal clinical trials. Overall, blocking the IL-17A pathway seems to have a positive effect on the bone and cartilage damage observed in inflammatory arthritis. Differences and specificity of these effects compared to those already described with other biologics such as anti-TNF therapies remain to be explored.

Intracytoplasmic expression of IL-6 and IL-17A in circulating CD4+ T cells are strongly associated with and predict disease activity in rheumatoid arthritis: A case-control study in Ghana

“…This nding is partly consistent with a study by Li et al [27] who found a direct relationship between IL-17A and DAS28 scores in rheumatoid arthritis patients. Indeed, high IL-6 and IL-17 has been implicated in higher DAS28 scores, which together correlate with radiographical progression of RA patients [28][29][30][31]. Nonetheless, contrary to our study, Chung et al [32], using enzyme-linked immunosorbent assay, reported no signi cant correlation between IL-6 and DAS28 scores.…”

Intracytoplasmic Expression of IL-6 and IL-17A in Circulating CD4+ T Cells Are Strongly Associated with and Predict Disease Activity in Rheumatoid Arthritis: A Case-Control Study in Ghana

“…This finding is partly consistent with a study by Li et al [ 32 ] who found a direct relationship between IL-17A and DAS28 scores in rheumatoid arthritis patients. Indeed, high IL-6 and IL-17 have been implicated in higher DAS28 scores, which together correlate with radiographical progression of RA patients [ 33 – 36 ]. Nonetheless, contrary to our study, Chung et al [ 37 ], using enzyme-linked immunosorbent assay, reported no significant correlation between IL-6 and DAS28 scores.…”

Regulatory Roles of Bone in Neurodegenerative Diseases

“…In postmenopausal osteoporosis patients, serum IL-17A is significantly higher, while the IFN-γ and IL-4 are significantly lower, suggesting osteoporosis may be more associated with the Th17 cells rather than the Th1 or Th2 cells (Zhang et al, 2015 ). The further study demonstrates IL-17A is pro-osteoclastogenic at the cellular level (Le Goff et al, 2019 ). In vivo study shows that although IL-17A is not required for normal bone homeostasis, it plays a vital role in bone loss of ovariectomized osteoporosis mouse models.…”

“…In vivo study shows that although IL-17A is not required for normal bone homeostasis, it plays a vital role in bone loss of ovariectomized osteoporosis mouse models. Furthermore, preliminary data from clinical trials show that anti-IL-17A antibodies stabilize bone density in inflammatory arthritis (Le Goff et al, 2019 ). These results suggest an inter-relationship between osteoporosis and neurodegenerative diseases.…”