Abstract
We aimed to evaluate the direct action of VIP on crucial molecules involved in human osteoclast differentiation and function. We also investigated the relationship between VIP serum levels and bone remodeling mediators in early arthritis patients. The expression of VIP receptors and osteoclast gene markers in monocytes and in vitro differentiated osteoclasts was studied by real-time PCR. NFATc1 activity was measured using a TransAM® kit. Osteoclastogenesis was confirmed by quantification of tartrate-resistant acid phosphatase positive multinucleated cells. OsteoAssay® Surface Multiple Well Plate was used to evaluate bone-resorbing activity. The ring-shaped actin cytoskeleton and the VPAC1 and VPAC2 expression were analyzed by immunofluorescence. We described the presence of VIP receptors in monocytes and mature osteoclasts. Osteoclasts that formed in the presence of VIP showed a decreased expression of osteoclast differentiation gene markers and proteolytic enzymes involved in bone resorption. VIP reduced the resorption activity and decreased both β3 integrin expression and actin ring formation. Elevated serum VIP levels in early arthritis patients were associated with lower BMD loss and higher serum OPG concentration. These results demonstrate that VIP exerts an anti-osteoclastogenic action impairing both differentiation and resorption activity mainly through the negative regulation of NFATc1, evidencing its bone-protective effects in humans.
Highlights
Introduction iationsBone remodeling maintains skeletal integrity thanks to the coordinated activity of osteoclasts and osteoblasts
Since the primary hypothesis underlying our study was the existence of a direct effect of vasoactive intestinal peptide (VIP) on human osteoclastogenesis and osteoclast function, we decided first to map the expression of VIP receptors in human osteoclast precursors isolated from both healthy donors and early arthritis patients, and in the respective mature osteoclast differentiated in vitro
The results showed a generalized reduction in the expression of VIP receptors genes in mature osteoclast
Summary
Introduction iationsBone remodeling maintains skeletal integrity thanks to the coordinated activity of osteoclasts and osteoblasts. When the activity of these cells is uncoupled, the physiological balance between bone resorption and formation is altered, with pathological repercussions on bone tissue [1,2]. Such is the case of rheumatoid arthritis (RA), an inflammatory autoimmune disease characterized by a chronic inflammation of the diarthrodial joints and articular bone erosions, mainly attributed to the hyperactivation of osteoclasts [3,4]. The resorptive activity of mature osteoclasts is initiated with their adhesion to bone matrix. This process is Licensee MDPI, Basel, Switzerland
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