title: Psoriatic cutaneous inflammation promotes human monocyte differentiation into active osteoclasts, facilitating bone damage.
abstract: Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy that can be associated with focal bone erosions. Psoriasis usually precedes the psoriatic arthritis onset by an average of 10 years, but this relation is not yet fully elucidated. Pro-inflammatory cytokines, such as IL-33, OPN, IL-17, and TNF-α are involved in both psoriasis and PsA pathogenesis as well as in bone homeostasis. In this study, we have demonstrated that IL-33, OPN, IL-17, and TNF-α induced the release of a wide range of pro-osteoclastogenic factors from the skin, such as RANKL, that promote monocyte differentiation in osteoclasts. The addition of osteoprotegerin, a RANKL inhibitor, to monocyte cultures treated with supernatant from stimulated skin did not completely deplete osteoclast formation, suggesting that skin produced several additional pro-osteoclastogenic mediators, which could act in a RANKL-independent manner. Moreover, we have found that RANKL serum levels as well as osteoclast number and activity in psoriatic patients with and without arthritis, was influenced by severity of cutaneous disease. Our data demonstrate that psoriatic cutaneous inflammation contributes to bone damage.
authors.affiliation: Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy.
authors.forename: Annunziata
authors.initials: A
authors.lastname: Raimondo
authors.affiliation: Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Lembo
authors.affiliation: Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Di Caprio
authors.affiliation: Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples, Napoli, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Donnarumma
authors.affiliation: Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Monfrecola
authors.affiliation: Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Balato
authors.affiliation: Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ayala
authors.affiliation: Department of Advanced Biomedical Sciences, University of Naples Federico II, Napoli, Italy.
authors.forename: Anna
authors.identifier: 0000-0001-5485-0172
authors.initials: A
authors.lastname: Balato
mesh_terms: D000328:Adult; D015535:Arthritis, Psoriatic / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D001862:Bone Resorption; D001842:Bone and Bones / Q000166:cytology / Q000276:immunology / Q000473:pathology*; D016207:Cytokines / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D020381:Interleukin-17 / Q000378:metabolism / Q000494:pharmacology; D000067596:Interleukin-33 / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D010010:Osteoclasts / Q000276:immunology / Q000502:physiology*; D010012:Osteogenesis; D053495:Osteopontin / Q000276:immunology; D053244:Osteoprotegerin / Q000097:blood; D011565:Psoriasis / Q000276:immunology* / Q000503:physiopathology; D053245:RANK Ligand / Q000097:blood / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; C506536:IL33 protein, human; D020381:Interleukin-17; D000067596:Interleukin-33; D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; D053495:Osteopontin
keywords: Bone erosion; Osteoclastogenesis; Osteoclasts; Psoriasis; Psoriatic arthritis