OP0241 IL9 MODULATION OF OSTEOCLASTS DIFFERENTIATION AND IMPACTS ON BONE METABOLISM

Background:Osteoclasts are multinucleated cells originating from the monocytes/macrophage lineage and require receptor activator of NF-κB ligand (RANK-L) and macrophage-colony-stimulating factor (M-CSF) for their development. They play a major role in bone remodeling by degrading the calcified bone matrix. They are considered as one of the culprits in bone destruction in many inflammatory diseases e.g. rheumatoid arthritis and osteoporosis. In previous work by our group, it was observed that IL-9 mediated the resolution of inflammation in rheumatoid arthritis and hence protected against bone degradation in animal models. Despite this protection was particularly associated to the resolution of inflammation, our data also supported the hypothesis of a direct signalling of IL-9 to osteoclasts.Objectives:The aim of this study was to investigate the modulating effect of IL-9 on osteoclasts and on the bone metabolism.Methods:Osteoclasts differentiation was studied in the mouse models of antigen induced arthritis (AIA) and KBxN serum induced arthritis (SIA) in the presence and absence of IL-9 by histomorphometric analysis and microcomputed tomography scans (µCT). Osteoclasts were generated from bone marrow derived monocytes of BALB/c mice with M-CSF, RANKL and IL-9, which were added in varying concentrations to induce osteoclast differentiation. Tartrate-resistant acid phosphatase (TRAP) staining was performed to follow the differentiation steps from monocytes into multinucleated osteoclasts and to determine the effects of IL-9 on osteoclastogenesis. Additionally, we performed RNA-seq and seahorse analysis to detect IL-9 dependent, differentially expressed genes and metabolites. Intracellular signaling as induced by IL9R activation was followed by western blot analysis.Results:IL-9 KO mice showed higher numbers of osteoclasts as compared to wild-type mice in the mouse models of AIA and SIA. Microcomputed tomography showed pronounced loss of the trabecular network and bone volume as signs of inflammation-induced osteopenia in Il9−/− mice. We found that osteoclasts express high levels of IL-9R. Next, monocytes were differentiated into osteoclasts in the presence of different concentrations of recombinant IL-9. Cells cultured in the presence of IL-9 showed significantly impaired differentiation into osteoclasts. We observed phosphorylation of STAT3 and STAT5 in cultured osteoclasts in dependency of IL-9. Furthermore, the presence of IL-9 during osteoclast differentiation impacted the gene expression levels of characteristic osteoclast related genes such as NFATc1, Cathepsin K and TRAP. Furthermore, IL-9 showed a major impact on mitochondrial respiration rate and glycolysis as assessed by Seahorse assays.Conclusion:IL-9 exerted direct effects on osteoclast differentiation and modulated the expression of several genes that are related to osteoclast differentiation and function.Disclosure of Interests:mina saad: None declared, Simon Rauber: None declared, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Andreas Ramming Grant/research support from: Pfizer, Novartis, Consultant of: Boehringer Ingelheim, Novartis, Gilead, Pfizer, Speakers bureau: Boehringer Ingelheim, Roche, Janssen

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Toll-like receptor 7 regulates osteoclastogenesis in rheumatoid arthritis

The Journal of Biochemistry ◽

10.1093/jb/mvz033 ◽

2019 ◽

Vol 166 (3) ◽

pp. 259-270 ◽

Cited By ~ 2

Author(s):

Kyoung-Woon Kim ◽

Bo-Mi Kim ◽

Ji-Yeon Won ◽

Kyung-Ann Lee ◽

Hae-Rim Kim ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Osteoclast Differentiation ◽

Bone Destruction ◽

Synovial Fibroblasts ◽

Enzyme Linked Immunosorbent Assay ◽

Signal Molecules ◽

Signal Pathways ◽

Tartrate Resistant Acid Phosphatase ◽

Toll Like Receptor ◽

Multinucleated Cells

Abstract This study aimed to determine the regulatory role of toll-like receptor 7 (TLR7) in receptor activator of nuclear factor kappa-B ligand (RANKL) production and osteoclast differentiation in rheumatoid arthritis (RA). In confocal microscopy, the co-expression of TLR7, CD55 and RANKL was determined in RA synovial fibroblasts. After RA synovial fibroblasts were treated with imiquimod, the RANKL gene expression and protein production were determined by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Osteoclastogenesis from peripheral blood CD14+ monocytes which were cultured with imiquimod was assessed by determining the numbers of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. The signal pathways mediating the TLR7-induced RANKL expression and osteoclastogenesis were analysed after inhibition of intracellular signal molecules and their phosphorylation. Imiquimod stimulated the expression of TLR7 and RANKL and production of RANKL in RA synovial fibroblasts, increasing the phosphorylation of TRAF6, IRF7, mitogen-activated protein kinases (MAPK), c-Jun and NFATc1. When CD14+ monocytes were cultured with imiquimod or co-cultured with imiquimod-pre-treated RA synovial fibroblasts, they were differentiated into TRAP+ multinucleated osteoclasts in the absence of RANKL. TLR7 activation-induced osteoclastogenesis in RA through direct induction of osteoclast differentiation from its precursors and up-regulation of RANKL production in RA synovial fibroblasts. Thus, the blockage of TLR7 pathway could be a promising therapeutic strategy for preventing bone destruction in RA.

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The Impact of Proinflammatory Cytokynes of Rheumatoid Polyarthritis on the Generalized Loss of Bone Mass

Revista de Chimie ◽

10.37358/rc.18.9.6572 ◽

2018 ◽

Vol 69 (9) ◽

pp. 2541-2545

Author(s):

Raluca Barzoi ◽

Elena Rezus ◽

Codruta Badescu ◽

Razan Al Namat ◽

Manuela Ciocoiu

Keyword(s):

Rheumatoid Arthritis ◽

Immune Cells ◽

Osteoclast Differentiation ◽

Bone Destruction ◽

Nuclear Factor ◽

Receptor Activator ◽

Level Function ◽

Rheumatoid Polyarthritis ◽

The Impact ◽

Nuclear Factor Kb

There is a bidirectional interaction between most immune cells and osteoblasts, osteoclasts and their precursor cells. The receptor activator of nuclear factor-kB ligand (RANKL)/RANK/osteoprotegerin (OPG) system plays an essential role in the formation of osteoblasts, but it also has implications in osteoclast biology and implicitly on the diseases characterized by bone loss. Proinflammatory cytokines existing at synovial level function as direct or indirect stimulators of osteoclast differentiation, but also of its survival or activity, although some cytokines may also play an antiosteocastogenic role. The fate of bone destruction is determined by the balance between osteoclastogenic and antiosteoclastogenic mediators. Our study has shown that the early initiation of the therapy with anti-TNF and anti-IL6 biological agents, in patients with rheumatoid arthritis, inhibits bone destruction, regardless of the anti-inflammatory activity in patients with rheumatoid arthritis.

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Promotion of osteoclastogenesis by IL-26 in rheumatoid arthritis

Arthritis Research & Therapy ◽

10.1186/s13075-019-2070-0 ◽

2019 ◽

Vol 21 (1) ◽

Author(s):

Kyung-Ann Lee ◽

Kyoung-Woon Kim ◽

Bo-Mi Kim ◽

Ji-Yeon Won ◽

Hong Ki Min ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Peripheral Blood ◽

Osteoclast Differentiation ◽

Joint Damage ◽

Enzyme Linked Immunosorbent Assay ◽

Tartrate Resistant Acid Phosphatase ◽

Dependent Manner ◽

Receptor Subunit ◽

Blood Monocytes ◽

Peripheral Blood Monocytes

Abstract Background The inflammatory cascade in the rheumatoid arthritis (RA) synovium is modulated by a variety of cytokine and chemokine networks; however, the roles of IL-26, in RA pathogenesis, are poorly defined. Here, we investigated the functional role of interleukin-26 (IL)-26 in osteoclastogenesis in RA. Methods We analyzed levels of IL-20 receptor subunit A (IL-20RA), CD55, and receptor activator of nuclear factor kappaB (NF-κB) ligand (RANKL) in RA fibroblast-like synoviocytes (FLSs) using confocal microscopy. Recombinant human IL-26-induced RANKL expression in RA-FLSs was examined using real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Human peripheral blood monocytes were cultured with macrophage colony-stimulating factor (M-CSF) and IL-26, after which osteoclastogenesis was evaluated by counting the number of tartrate-resistant acid phosphatase-positive multinucleated cells. Additionally, osteoclastogenesis was evaluated by monocytes co-cultured with IL-26-prestimulated FLSs. Results The expression of IL-20RA in RA-FLSs was higher than that in osteoarthritis-FLSs. Additionally, in IL-26-pretreated RA-FLSs, the expression of IL-20RA (but not IL-10 receptor subunit B) and RANKL increased in a dose-dependent manner, with IL-26-induced RANKL expression reduced by IL-20RA knockdown. Moreover, IL-26-induced RANKL expression was significantly downregulated by inhibition of signal transducer and activator of transcription 1, mitogen-activated protein kinase, and NF-κB signaling. Furthermore, IL-26 promoted osteoclast differentiation from peripheral blood monocytes in the presence of low dose of RANKL, with IL-26 exerting an additive effect. Furthermore, co-culture of IL-26-pretreated RA-FLSs with peripheral blood monocytes also increased osteoclast differentiation in the absence of addition of RANKL. Conclusions IL-26 regulated osteoclastogenesis in RA through increased RANKL expression in FLSs and direct stimulation of osteoclast differentiation. These results suggest the IL-26/IL-20RA/RANKL axis as a potential therapeutic target for addressing RA-related joint damage.

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CD14+CD16− monocytes are the main precursors of osteoclasts in rheumatoid arthritis via expressing Tyro3TK

Arthritis Research & Therapy ◽

10.1186/s13075-020-02308-7 ◽

2020 ◽

Vol 22 (1) ◽

Author(s):

Jimeng Xue ◽

Liling Xu ◽

Huaqun Zhu ◽

Mingxin Bai ◽

Xin Li ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Tyrosine Kinase ◽

Osteoclast Differentiation ◽

Tender Joint Count ◽

Tartrate Resistant Acid Phosphatase ◽

Dependent Manner ◽

Monocyte Subsets ◽

Tender Joint ◽

Critical Signal

Abstract Background Monocytes as precursors of osteoclasts in rheumatoid arthritis (RA) are well demonstrated, while monocyte subsets in osteoclast formation are still controversial. Tyro3 tyrosine kinase (Tyro3TK) is a member of the receptor tyrosine kinase family involved in immune homeostasis, the role of which in osteoclast differentiation was reported recently. This study aimed to compare the osteoclastic capacity of CD14+CD16+ and CD14+CD16− monocytes in RA and determine the potential involvement of Tyro3TK in their osteoclastogenesis. Methods Osteoclasts were induced from CD14+CD16+ and CD14+CD16− monocyte subsets isolated from healthy control (HC) and RA patients in vitro and evaluated by tartrate-resistant acid phosphatase (TRAP) staining. Then, the expression of Tyro3TK on CD14+CD16+ and CD14+CD16− monocyte subsets in the peripheral blood of RA, osteoarthritis (OA) patients, and HC were evaluated by flow cytometry and qPCR, and their correlation with RA patient clinical and immunological features was analyzed. The role of Tyro3TK in CD14+CD16− monocyte-mediated osteoclastogenesis was further investigated by osteoclast differentiation assay with Tyro3TK blockade. Results The results revealed that CD14+CD16− monocytes were the primary source of osteoclasts. Compared with HC and OA patients, the expression of Tyro3TK on CD14+CD16− monocytes in RA patients was significantly upregulated and positively correlated with the disease manifestations, such as IgM level, tender joint count, and the disease activity score. Moreover, anti-Tyro3TK antibody could inhibit Gas6-mediated osteoclast differentiation from CD14+CD16− monocytes in a dose-dependent manner. Conclusions These findings indicate that elevated Tyro3TK on CD14+CD16− monocytes serves as a critical signal for osteoclast differentiation in RA.

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Monosodium Urate in the Presence of RANKL Promotes Osteoclast Formation through Activation of c-Jun N-Terminal Kinase

Mediators of Inflammation ◽

10.1155/2015/597512 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 11

Author(s):

Jung-Yoon Choe ◽

Ki-Yeun Park ◽

Seong-Kyu Kim

Keyword(s):

Osteoclast Differentiation ◽

Tumor Necrosis Factor Receptor ◽

Bone Destruction ◽

Cathepsin K ◽

Osteoclast Formation ◽

Response To Treatment ◽

Tartrate Resistant Acid Phosphatase ◽

Raw 264.7 ◽

Monosodium Urate ◽

Msu Crystals

The aim of this study was to clarify the role of monosodium urate (MSU) crystals in receptor activator of nuclear factor kB ligand- (RANKL-) RANK-induced osteoclast formation. RAW 264.7 murine macrophage cells were incubated with MSU crystals or RANKL and differentiated into osteoclast-like cells as confirmed by staining for tartrate-resistant acid phosphatase (TRAP) and actin ring, pit formation assay, and TRAP activity assay. MSU crystals in the presence of RANKL augmented osteoclast differentiation, with enhanced mRNA expression of NFATc1, cathepsin K, carbonic anhydrase II, and matrix metalloproteinase-9 (MMP-9), in comparison to RAW 264.7 macrophages incubated in the presence of RANKL alone. Treatment with both MSU crystals and RANKL induced osteoclast differentiation by activating downstream molecules in the RANKL-RANK pathway including tumor necrosis factor receptor-associated factor 6 (TRAF-6), JNK, c-Jun, and NFATc1. IL-1b produced in response to treatment with both MSU and RANKL is involved in osteoclast differentiation in part through the induction of TRAF-6 downstream of the IL-1b pathway. This study revealed that MSU crystals contribute to enhanced osteoclast formation through activation of RANKL-mediated pathways and recruitment of IL-1b. These findings suggest that MSU crystals might be a pathologic causative agent of bone destruction in gout.

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Propionibacterium freudenreichii Inhibits RANKL-Induced Osteoclast Differentiation and Ameliorates Rheumatoid Arthritis in Collagen-Induced Arthritis Mice

Microorganisms ◽

10.3390/microorganisms10010048 ◽

2021 ◽

Vol 10 (1) ◽

pp. 48

Author(s):

Jiah Yeom ◽

Dong Joon Yim ◽

Seongho Ma ◽

Young-Hee Lim

Keyword(s):

Rheumatoid Arthritis ◽

Mouse Model ◽

Bone Erosion ◽

Osteoclast Differentiation ◽

Joint Damage ◽

Bone Destruction ◽

In Vivo Studies ◽

Propionibacterium Freudenreichii ◽

Limited Information ◽

Collagen Induced Arthritis

Osteoclast differentiation is crucial for bone absorption, and osteoclasts are involved in bone destruction in rheumatoid arthritis (RA). Dairy Propionibacterium freudenreichii is used as a cheese starter and possesses prebiotic and postbiotic properties. It is known to stimulate the growth of bifidobacteria and produces valuable metabolites, such as vitamin B12 and propionic acid. However, limited information is available on the beneficial effects of P. freudenreichii on human disease. Herein, we aimed to investigate the inhibitory effect of P. freudenreichii MJ2 (MJ2) isolated from raw milk on osteoclast differentiation and evaluate the improvement in RA. The murine macrophage cell line, RAW 264.7, and a collagen-induced arthritis (CIA) mouse model were used to perform in vitro and in vivo studies, respectively. Heat-killed P. freudenreichii MJ2 (hkMJ2)-treated cells significantly inhibited RANKL-induced osteoclast differentiation and TRAP activity. HkMJ2-treated cells exhibited significantly decreased expression of genes and proteins related to RANKL-induced osteoclast differentiation. MJ2 administration decreased the arthritic score in the CIA mouse model. Live and dead MJ2 inhibited bone loss and afforded protection against bone erosion and joint damage in CIA mice. MJ2 decreased the levels of collagen-specific antibodies and inflammatory cytokines and the expression of osteoclast differentiation-related genes and proteins in CIA mice. Interestingly, live and dead MJ2 showed similar RA improvement effects in CIA mice. In conclusion, P. freudenreichii MJ2 inhibited osteoclast differentiation by inhibiting the NF-κB signaling pathway and ameliorated CIA.

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Interleukin (IL)-25 suppresses IL-22 induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway

10.21203/rs.2.19355/v2 ◽

2020 ◽

Author(s):

Hong Ki Min ◽

Ji-Yeon Won ◽

Bo-Mi Kim ◽

Kyung-Ann Lee ◽

Seoung-Joon Lee ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fluid ◽

P38 Mapk ◽

Human Peripheral Blood ◽

Osteoclast Differentiation ◽

Nuclear Factor Κb ◽

Enzyme Linked Immunosorbent Assay ◽

Tartrate Resistant Acid Phosphatase ◽

Blood Monocytes ◽

Rankl Expression

Abstract Background The present study aimed to evaluate the suppressive role of interleukin (IL)-25 in IL-22-induced osteoclastogenesis and receptor activator of nuclear factor κB ligand (RANKL) expression in rheumatoid arthritis (RA). Methods Serum from patients with RA and osteoarthritis (OA), and healthy controls, as well as synovial fluid from patients with RA and OA were collected, and the levels of IL-22 and IL-25 were measured. RA and OA synovial tissues were stained against IL-25. Fibroblast-like synoviocytes (FLSs) of patients with RA were cultured with IL-22, in the presence or absence of IL-25, and RANKL expression was measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Human peripheral blood monocytes were cultured under IL-22/RANKL + M-CSF, with or without IL-25, and tartrate-resistant acid phosphatase (TRAP)-positive cells and osteoclast-related markers were investigated to determine osteoclastogenesis. Results Serum and synovial IL-25 levels in RA were up-regulated compared to those in OA and healthy control, and elevated expression of IL-25 in RA synovial tissue was re-confirmed. IL-25 and IL-22 levels showed significant correlation in serum and synovial fluid. Pre-treatment of FLS with IL-25 reduced IL-22-induced RANKL expression at the RNA level. The suppressive effects of IL-25 were confirmed to occur through the STAT3 and p38 MAPK/IκBα pathways. IL-25 reduced osteoclast differentiation and suppressed the expression of osteoclast-related markers. Conclusion In the current study, we demonstrated the regulatory effect of IL-25 on IL-22-induced osteoclastogenesis. Therapeutic approach involving augmentation of IL-25 regulatory response may serve as a novel treatment option for RA, especially by suppressing osteoclastogenesis.

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Identification of Two-pore Channel 2 as a Novel Regulator of Osteoclastogenesis

Journal of Biological Chemistry ◽

10.1074/jbc.m111.328930 ◽

2012 ◽

Vol 287 (42) ◽

pp. 35057-35064 ◽

Cited By ~ 18

Author(s):

Takuya Notomi ◽

Yoichi Ezura ◽

Masaki Noda

Keyword(s):

Acid Phosphatase ◽

Nuclear Localization ◽

Intracellular Signaling ◽

Osteoclast Differentiation ◽

Pore Channel ◽

Tartrate Resistant Acid Phosphatase ◽

Pit Formation ◽

Control Bone ◽

Key Events ◽

Mrna Expression Levels

Osteoclast differentiation is one of the critical steps that control bone mass levels in osteoporosis, but the molecules involved in osteoclastogenesis are still incompletely understood. Here, we show that two-pore channel 2 (TPC2) is expressed in osteoclast precursor cells, and its knockdown (TPC2-KD) in these cells suppressed RANKL-induced key events including multinucleation, enhancement of tartrate-resistant acid phosphatase (TRAP) activities, and TRAP mRNA expression levels. With respect to intracellular signaling, TPC2-KD reduced the levels of the RANKL-induced dynamic waving of Ca2+ in RAW cells. The search for the target of TPC2 identified that nuclear localization of NFATc1 is retarded in TPC2-KD cells. Finally, TPC2-KD suppressed osteoclastic pit formation in cultures. We conclude that TPC2 is a novel critical molecule for osteoclastogenesis.

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Serum Heme Oxygenase-1 and BMP-7 Are Potential Biomarkers for Bone Metabolism in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

BioMed Research International ◽

10.1155/2016/7870925 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Tong-ling Yuan ◽

Jin Chen ◽

Yan-li Tong ◽

Yan Zhang ◽

Yuan-yuan Liu ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Ankylosing Spondylitis ◽

Bone Metabolism ◽

Bone Remodeling ◽

Heme Oxygenase ◽

Serum Levels ◽

Heme Oxygenase 1 ◽

Tartrate Resistant Acid Phosphatase ◽

Trap 5B ◽

Potential Biomarkers

Backgrounds. Heme oxygenase-1 (HO-1) has been reported to play a regulatory role in osteoclastogenesis. Bone morphogenetic protein (BMP) pathways induce osteoblastic differentiation and bone remodeling.Aims. To identify serum levels of HO-1, BMP-7, and Runt related-transcription factor 2 (Runx2) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to investigate the relationships between HO-1, BMP-7, Runx2, and other common biomarkers for bone metabolism.Results. Serum levels of HO-1 and BMP-7 were revealed to be significantly higher in patients with RA or AS than in healthy controls (p<0.01). In RA group, HO-1 was positively correlated with BMP-7, Runx2, and tartrate-resistant acid phosphatase-5b (TRAP-5b) (p<0.05, resp.), BMP-7 was positively correlated with Runx2 and TRAP-5b (p<0.05, resp.), and Runx2 was negatively correlated with N-terminal midfragment of osteocalcin (NMID) (p<0.05). In AS group, we observed identical correlation between HO-1 and BMP-7, but opposite correlations between BMP-7 and TRAP-5b and between Runx2 and NMID, when comparing with the RA cohort.Conclusion. Our findings suggest that HO-1 and BMP-7 are potential biomarkers for bone metabolism in patients with RA and AS. The different correlations between the bone markers point to distinct differences in bone remodeling pathways in the two types of arthritis.

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The dramatic role of IFN family in aberrant inflammatory osteolysis

Current Gene Therapy ◽

10.2174/1566523220666201127114845 ◽

2020 ◽

Vol 20 ◽

Author(s):

Zihan Deng ◽

Wenhui Hu ◽

Hongbo Ai ◽

Yueqi Chen ◽

Shiwu Dong

Keyword(s):

Bone Resorption ◽

Biological Activities ◽

Bone Matrix ◽

Osteoclast Differentiation ◽

Bone Destruction ◽

Bone Diseases ◽

Therapeutic Effects ◽

Type I ◽

Type Iii

: Skeletal system has been considered as a highly dynamic system, in which bone-forming osteoblasts and boneresorbing osteoclasts go through continuous remodeling cycle to maintain homeostasis of bone matrix. It has been well acknowledged that interferons (IFNs), acting as a subgroup of cytokines, not only make crucial effects on regulating immunology, but also could modulate the dynamic balance of bone matrix. In the light of different isoforms, IFNs have been divided into three major categories in terms of amino acid sequences, recognition of specific receptors and biological activities. Currently, type I IFNs consist of a multi-gene family with several subtypes, of which IFN-α exerts proosteoblastogenic effects to activate osteoblast differentiation and inhibits osteoclast fusion to maintain bone matrix integrity. Meanwhile, IFN-β suppresses osteoblast-mediated bone remodeling as well as exhibits inhibitory effects on osteoclast differentiation to attenuate bone resorption. While type II IFN constitutes the only type, IFN-γ, which exerts regulatory effects on osteoclastic bone resorption and osteoblastic bone formation by biphasic ways. Interestingly, type III IFNs are regarded as new members of IFN family composed of four members, including IFN-λ1 (IL-29), IFN-λ2 (IL-28A), IFN-λ3 (IL-28B) and IFN-λ4, which have been certified to participate in bone destruction. However, the direct regulatory mechanisms underlying how type III IFNs modulate metabolic balance of bone matrix remains poorly elucidated. In this review, we have summarized functions of IFN family during physiological and pathological conditions and described the mechanisms by which IFNs maintain bone matrix homeostasis via affecting the osteoclast-osteoblast crosstalk. In addition, the potential therapeutic effects of IFNs on inflammatory bone destruction diseases such as rheumatoid arthritis (RA), osteoarthritis (OA) and infectious bone diseases are also well displayed, which are based on the predominant role of IFNs in modulating the dynamic equilibrium of bone matrix.

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