Circulating mediators of bone remodeling in psoriatic arthritis: implications for disordered osteoclastogenesis and bone erosion.
BACKGROUND
Diverse bone pathologies are observed in patients with psoriatic arthritis (PsA). Uncoupling of bone remodeling with disordered osteoclastogenesis has been implicated in the pathogenesis of PsA. The aim of this study was to examine the role of soluble mediators of bone remodeling within the circulation of patients with PsA.


METHODS
Patients with PsA (n = 38), with psoriasis (n = 10), and healthy controls (n = 12) were studied. Serum was obtained for testing of Dikkopf-1 (Dkk-1), macrophage-colony stimulating factor (M-CSF), osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) with ELISA. Patients with PsA also had bone densitometry, plain radiographs of the hands and feet, and assessment of peripheral blood osteoclast precursors. Radiographs were scored for erosion, joint-space narrowing, osteolysis, and new bone formation.


RESULTS
Compared with those with psoriasis and healthy controls, patients with PsA had higher circulating concentrations of Dkk-1 and M-CSF. In patients with PsA, M-CSF and RANKL, but not Dkk-1, concentrations positively correlated with radiographic erosion, joint-space narrowing, and osteolysis scores. Mediators of bone remodeling did not correlate with the number of joints with new bone formation or with total hip-bone mineral density. Peripheral blood CD14+/CD11b+ cells, and the number of osteoclast-like cells and resorptive pits after culture with RANKL and M-CSF also correlated with radiographic damage scores. Circulating M-CSF concentrations correlated with the percentage of peripheral blood CD14+/CD11b+ cells.


CONCLUSIONS
Systemic expression of soluble factors that promote osteoclastogenesis is disordered in patients with PsA and may contribute to periarticular bone loss in this disease.
Dalbeth
Nicola
N
Department of Medicine, University of Auckland, Auckland 1010, New Zealand. n.dalbeth@auckland.ac.nz
Pool
Bregina
B
Smith
Timothy
T
Callon
Karen E
KE
Lobo
Maria
M
Taylor
William J
WJ
Jones
Peter B
PB
Cornish
Jillian
J
McQueen
Fiona M
FM
D000328:Adult; D000368:Aged; D015535:Arthritis, Psoriatic / Q000378:metabolism* / Q000473:pathology*; D015415:Biomarkers / Q000097:blood*; D016723:Bone Remodeling / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology*; D053244:Osteoprotegerin / Q000097:blood; D053245:RANK Ligand / Q000097:blood; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
D015415:Biomarkers; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D016173:Macrophage Colony-Stimulating Factor
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