n previous research studies, we demonstrated how psoriatic skin inflammation contributed to joint inflammation, and the resulting structural alterations of the bone, in a “pro-osteoclastogenic march”. Bone erosions depend on osteoclasts (OC), derived from monocytes-macrophages. A key element of the bone resorption process is the cytokine system consisting of the nuclear factor kappa-B activating receptor ligand (RANKL) and its receptor (RANK). OC maturation is a complex process involving several intracellular signaling pathways, including the cyclic AMP (cAMP) pathway. The latter’s intracellular concentration results from the balance between its synthesis, by adenylate cyclase, and its degradation, by PDEs. Apremilast, indicated for the treatment of psoriasis and PsA, is a selective inhibitor of PDE4. The objective of our study was to investigate the action of Apremilast therapy in the osteoclastogenesis process of patients with moderate-severe psoriasis. In this regard, patients suffering from moderate-severe psoriasis without arthritis who were candidates for systemic therapy with Apremilast were enrolled. At baseline and after 52 weeks of treatment, a blood sample was carried out for the in vitro evaluation of spontaneous osteoclastogenesis from monocytes-macrophages isolated from peripheral blood cells and the evaluation of serum levels of RANKL (main pro-osteoclastogenic mediator). The number of OC was significantly increased in psoriasis patients compared to healthy controls. After 52 weeks of treatment with Apremilast, the number of OC significantly decreased. Plasma RANKL concentration was significantly increased in psoriasis patients compared to controls. Furthermore, our results showed significantly reduced RANKL levels in patients with psoriasis after one year of treatment with Apremilast. The study provides new information on the role of PDE4 in the pro-osteoclastogenic process of the psoriatic patient with possible important clinical and therapeutic implications.
Psoriasis and bone damage: the role of phosphodiesterase 4 in the pro-osteoclastogenic process induced by skin inflammation.
Annunziata Raimondo;Alessia Balestrino;Serena Lembo
2024-01-01
Abstract
n previous research studies, we demonstrated how psoriatic skin inflammation contributed to joint inflammation, and the resulting structural alterations of the bone, in a “pro-osteoclastogenic march”. Bone erosions depend on osteoclasts (OC), derived from monocytes-macrophages. A key element of the bone resorption process is the cytokine system consisting of the nuclear factor kappa-B activating receptor ligand (RANKL) and its receptor (RANK). OC maturation is a complex process involving several intracellular signaling pathways, including the cyclic AMP (cAMP) pathway. The latter’s intracellular concentration results from the balance between its synthesis, by adenylate cyclase, and its degradation, by PDEs. Apremilast, indicated for the treatment of psoriasis and PsA, is a selective inhibitor of PDE4. The objective of our study was to investigate the action of Apremilast therapy in the osteoclastogenesis process of patients with moderate-severe psoriasis. In this regard, patients suffering from moderate-severe psoriasis without arthritis who were candidates for systemic therapy with Apremilast were enrolled. At baseline and after 52 weeks of treatment, a blood sample was carried out for the in vitro evaluation of spontaneous osteoclastogenesis from monocytes-macrophages isolated from peripheral blood cells and the evaluation of serum levels of RANKL (main pro-osteoclastogenic mediator). The number of OC was significantly increased in psoriasis patients compared to healthy controls. After 52 weeks of treatment with Apremilast, the number of OC significantly decreased. Plasma RANKL concentration was significantly increased in psoriasis patients compared to controls. Furthermore, our results showed significantly reduced RANKL levels in patients with psoriasis after one year of treatment with Apremilast. The study provides new information on the role of PDE4 in the pro-osteoclastogenic process of the psoriatic patient with possible important clinical and therapeutic implications.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
