The Critical Role of IL-34 in Osteoclastogenesis

Chen, Zhi; Büki, Kálmán G.; Vääräniemi, Jukka; Gu, Guoliang; Väänänen, H. Kalervo

doi:10.1371/journal.pone.0018689

Cited by 120 publications

(118 citation statements)

References 30 publications

(39 reference statements)

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“…The recently discovered cytokine IL-34 is an alternative ligand for the M-CSF receptor, and is now considered to constitute a novel non-canonical pathway of osteoclast formation, as it can substitute for M-CSF in osteoclast differentiation and play an important role in RANKL-induced osteoclastogenesis 9) . Patients with inflammatory periodontal disease often have elevated serum levels of proinflammatory cytokines 19) .…”

Section: Discussionmentioning

confidence: 99%

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Interleukin-34 Levels in Gingival Crevicular Fluid and Plasma in Healthy and Diseased Periodontal Tissue in Presence or Absence of Obesity: A Clinico-biochemical Study

Guruprasad

Pradeep

2018

Bull. Tokyo Dent. Coll.

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Interleukin (IL)-34 has recently been identified as an alternative ligand for colonystimulating factor-1 receptor and plays an important role in osteoclastogenesis. The aim of this study was to assess and compare IL-34 levels in gingival crevicular fluid (GCF) and plasma in obese individuals in the presence or absence of periodontal disease and to determine whether they showed a correlation with disease severity. Forty patients aged between 25 and 40 yr were enrolled and categorized into 4 groups: 10 non-obese patients with healthy periodontium (Group I); 10 obese patients with healthy periodontium (Group II); 10 non-obese patients with chronic periodontitis (Group III); and 10 obese patients with chronic periodontitis (Group IV). Demographic variables such as age and body mass index score were recorded and assessed, together with clinical periodontal parameters such as the gingival index, probing pocket depth, and clinical attachment level scores in all groups. The GCF and plasma levels of IL-34 were quantified using enzyme-linked immunosorbent assay. The results showed that the mean IL-34 concentrations in GCF or plasma were highest in Group IV, followed by Group III, Group II, and Group I, with the difference among them being statistically significant (p<0.05). These results suggest that obese individuals with periodontitis have higher GCF and plasma IL-34 levels than non-obese individuals with healthy periodontium. This suggests IL-34 as a potential inflammatory marker of periodontal disease and obesity.

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Section: Discussionmentioning

confidence: 99%

“…Interleukin-34 plays an important role in RANKL-induced osteoclastogenesis, as it can substitute for M-CSF and support osteoclast differentiation in the same way 9) . It is likely that IL-34 plays a role in inflammation, as it increases IL-6 and chemokine levels in human whole blood 11) .…”

Section: Introductionmentioning

confidence: 99%

Interleukin-34 Levels in Gingival Crevicular Fluid and Plasma in Healthy and Diseased Periodontal Tissue in Presence or Absence of Obesity: A Clinico-biochemical Study

Guruprasad

Pradeep

2018

Bull. Tokyo Dent. Coll.

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“…When IL-34 was expressed under the control of the CSF-1 promotor in CSF-1 op/op mice, the osteopetrotic phenotype was rescued (15). IL-34 in combination with RANKL induced osteoclastic differentiation of progenitor cells in mouse (16,17) and human (17) cell culture systems. However, it remains unclear why IL-34 cannot substitute for CSF-1 in CSF-1 op/op mice in vivo.…”

Section: ] (1 2)mentioning

confidence: 99%

Spleen serves as a reservoir of osteoclast precursors through vitamin D-induced IL-34 expression in osteopetrotic op/op mice

Nakamichi¹,

Mizoguchi²,

Arai³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Osteoclasts are generated from monocyte/macrophage-lineage precursors in response to colony-stimulating factor 1 (CSF-1) and receptor activator of nuclear factor-κB ligand (RANKL). CSF-1-mutated CSF-1 op/op mice as well as RANKL −/− mice exhibit osteopetrosis (OP) caused by osteoclast deficiency. We previously identified RANKL receptor (RANK)/CSF-1 receptor (CSF-1R) double-positive cells as osteoclast precursors (OCPs), which existed in bone in RANKL −/− mice. Here we show that OCPs do not exist in bone but in spleen in CSF-1 op/op mice, and spleen acts as their reservoir. IL-34, a newly discovered CSF-1R ligand, was highly expressed in vascular endothelial cells in spleen in CSF-1 op/op mice. Vascular endothelial cells in bone also expressed IL-34, but its expression level was much lower than in spleen, suggesting a role of IL-34 in the splenic generation of OCPs. Splenectomy (SPX) blocked CSF-1-induced osteoclastogenesis in CSF-1 op/op mice. Osteoclasts appeared in aged CSF-1 op/op mice with up-regulation of IL-34 expression in spleen and bone. Splenectomy blocked the age-associated appearance of osteoclasts. The injection of 2-methylene-19-nor-(20S)-1α,25(OH) 2 D 3 (2MD), a potent analog of 1α,25-dihidroxyvitamin D 3 , into CSF-1 op/op mice induced both hypercalcemia and osteoclastogenesis. Administration of 2MD enhanced IL-34 expression not only in spleen but also in bone through a vitamin D receptor-mediated mechanism. Either splenectomy or siRNA-mediated knockdown of IL-34 suppressed 2MD-induced osteoclastogenesis. These results suggest that IL-34 plays a pivotal role in maintaining the splenic reservoir of OCPs, which are transferred to bone in response to diverse stimuli, in CSF-1 op/op mice. The present study also suggests that the IL-34 gene in vascular endothelial cells is a unique target of vitamin D. CSF-1 is the most potent growth factor for monocytes/macrophages (3), but its synthesis by osteoblasts occurs independently of PTH and 1α,25(OH) 2 D 3 (2). CSF-1 op/op mice cannot produce a functionally active CSF-1 (4), and therefore, exhibit monocytopenia and osteopetrosis (OP) (5, 6). However, several curious phenomena have been observed in CSF-1 op/op mice. First, osteoclasts are totally absent in young CSF-1 op/op mice, but appear in aged CSF-1 op/op mice (7). Second, osteopetrotic characteristics of CSF-1R −/− mice are more severe than those of CSF-1 op/op mice (8). Third, F4/80 + [F4/80(+)] macrophages exist in the splenic red pulp in CSF-1 op/op mice as well as in WT mice, and their number is regulated by a mechanism independently of CSF-1 (9, 10). Fourth, the administration of vascular endothelial growth factor (VEGF) rescues osteopetrosis in CSF-1 op/op mice (11, 12), but VEGF cannot substitute for CSF-1 to induce osteoclast formation in vitro (13).Recently, Lin et al. (14) discovered IL-34, as a new ligand for CSF-1R. The amino acid sequence of IL-34 was quite different from that of CSF-1, but IL-34 promoted macrophage colony formation like CSF-1 did. IL-34 was specifically expressed in splen...

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“…Eda et al, documented that IL-34 could increase IL-6 and chemokine levels in human whole blood [12]. It also could promote osteoclastogenesis in vitro [13]. Tian et al, found that IL-34 expression could be induced by TNF-α and IL-1β which are pivotal cytokines in RA [14].…”

Section: Introductionmentioning

confidence: 99%

Joint Destruction and Osteoporosis are Associated with Upregulation of IL34 and Cathepsin k Expression in Rheumatoid Arthritis. Clinical Trial with Anti TNF ÃÂ± Therapy

Atef¹,

Aziz²

2015

J Arthritis

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The Critical Role of IL-34 in Osteoclastogenesis

Cited by 120 publications

References 30 publications

Interleukin-34 Levels in Gingival Crevicular Fluid and Plasma in Healthy and Diseased Periodontal Tissue in Presence or Absence of Obesity: A Clinico-biochemical Study

Interleukin-34 Levels in Gingival Crevicular Fluid and Plasma in Healthy and Diseased Periodontal Tissue in Presence or Absence of Obesity: A Clinico-biochemical Study

Spleen serves as a reservoir of osteoclast precursors through vitamin D-induced IL-34 expression in osteopetrotic op/op mice

Joint Destruction and Osteoporosis are Associated with Upregulation of IL34 and Cathepsin k Expression in Rheumatoid Arthritis. Clinical Trial with Anti TNF ÃÂ± Therapy

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The Critical Role of IL-34 in Osteoclastogenesis

Cited by 120 publications

References 30 publications

Interleukin-34 Levels in Gingival Crevicular Fluid and Plasma in Healthy and Diseased Periodontal Tissue in Presence or Absence of Obesity: A Clinico-biochemical Study

Interleukin-34 Levels in Gingival Crevicular Fluid and Plasma in Healthy and Diseased Periodontal Tissue in Presence or Absence of Obesity: A Clinico-biochemical Study

Spleen serves as a reservoir of osteoclast precursors through vitamin D-induced IL-34 expression in osteopetrotic op/op mice

Joint Destruction and Osteoporosis are Associated with Upregulation of IL34 and Cathepsin k Expression in Rheumatoid Arthritis. Clinical Trial with Anti TNF ÃÂ± Therapy

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Joint Destruction and Osteoporosis are Associated with Upregulation of IL34 and Cathepsin k Expression in Rheumatoid Arthritis. Clinical Trial with Anti TNF ÃÂ± Therapy