Abstract
Recently, it was shown that interleukin-1β (IL-1β) has diverse stimulatory effects on different murine long bone marrow osteoclast precursors (OCPs) in vitro. In this study, interleukin-1 receptor antagonist deficient (Il1rn−/−) and wild-type (WT) mice were compared to investigate the effects of enhanced IL-1 signaling on the composition of OCPs in long bone, calvaria, vertebra, and jaw. Bone marrow cells were isolated from these sites and the percentage of early blast (CD31hi Ly-6C−), myeloid blast (CD31+ Ly-6C+), and monocyte (CD31− Ly-6Chi) OCPs was assessed by flow cytometry. At the time-point of cell isolation, Il1rn−/− mice showed no inflammation or bone destruction yet as determined by histology and microcomputed tomography. However, Il1rn−/− mice had an approximately two-fold higher percentage of OCPs in long bone and jaw marrow compared to WT. Conversely, vertebrae and calvaria marrow contained a similar composition of OCPs in both strains. Bone marrow cells were cultured with macrophage colony stimulating factor (M-CSF) and receptor of NfκB ligand (RANKL) on bone slices to assess osteoclastogenesis and on calcium phosphate-coated plates to analyze mineral dissolution. Deletion of Il1rn increased osteoclastogenesis from long bone, calvaria, and jaw marrows, and all Il1rn−/− cultures showed increased mineral dissolution compared to WT. However, osteoclast markers increased exclusively in Il1rn−/− osteoclasts from long bone and jaw. Collectively, these findings indicate that a lack of IL-1RA increases the numbers of OCPs in vivo, particularly in long bone and jaw, where rheumatoid arthritis and periodontitis develop. Thus, increased bone loss at these sites may be triggered by a larger pool of OCPs due to the disruption of IL-1 inhibitors.
Highlights
Osteoclasts are multinucleated bone-resorbing cells that are essential for the homeostasis of bone
It has been reported that patients with active rheumatoid arthritis have a significantly increased chance of developing periodontitis when compared with healthy controls and that patients with periodontal disease have a higher incidence of rheumatoid arthritis than patients without periodontitis [2,3]
Both diseases are associated with inflammation and high levels of proinflammatory cytokines, such as interleukins 1 α and β (IL-1α, β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α)
Summary
Osteoclasts are multinucleated bone-resorbing cells that are essential for the homeostasis of bone. Shifting the balance in bone turnover favoring osteoclasts may result in excessive bone destruction in diseases like rheumatoid arthritis, osteoporosis, and periodontitis as reviewed for these diseases in [1]. It has been reported that patients with active rheumatoid arthritis have a significantly increased chance of developing periodontitis when compared with healthy controls and that patients with periodontal disease have a higher incidence of rheumatoid arthritis than patients without periodontitis [2,3] Both diseases are associated with inflammation and high levels of proinflammatory cytokines, such as interleukins 1 α and β (IL-1α, β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α). IL-1β has been shown to strongly stimulate osteoclastogenesis and bone resorption [4,5,6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: 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.
