Abstract
Abstract Bone loss is associated with osteoclasts (OC). We reported the development of OC from CD11c+dendritc cells (DDOC) via RANKL & Aggregatibacter actinomycetemcomitans (Aa) stimuli [J.Immunol/JBMR]. We aimed to study: i) proliferation, frequency & osteoclastogenic potential of DDOC in-vivo; ii) identify regulators of DDOC-development. CFU & limiting-dilution-analyses showed that CD11c+DDOC did not manifest detectable proliferation with an estimated OCp frequency 3+0.06% based on TRAP+multinucleated-OC. To assess their physiological relevance, CFSE-CD11c+DC were transferred onto NOD/SCID calvarias with Aa+IFA. By q-IHC, higher numbers of CFSE+CD11c+TRAP+OC were detected, in association with more bone-erosion in mice receiving DC, suggesting that CD11c+DC become TRAP+functional-OC under inflammation in-vivo. Moreover, the number of CD11c+TRAP+ multinucleated-OC was highly correlated with bone-loss on sub-chondral bone of collagen-induced arthritic joints in DBA-mice & Aa-induced periodontitis. Micro-arrays, RT-PCR & flow-cytometry were employed to identify regulator(s) in DDOC-development, demonstrating a (+)-correlation with TGF-RbII expression. Neutralization of TGF-b abolished DDOC development, based on TRAP & resorptive-pit assays in-vitro/in-vivo. These data support that: i) CD11c+DC subset(s) can act as OCp during inflammation; ii) TGF-RbII is essential for DDOC-development, an integral mechanism underlying inflammation-induced osteoclastogenesis at osteo-immune interface.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.