Bone as a Target Organ in Rheumatic Disease: Impact on Osteoclasts and Osteoblasts

Baum, Rebecca; Gravallese, Ellen M.

doi:10.1007/s12016-015-8515-6

Cited by 83 publications

(79 citation statements)

References 159 publications

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“…Progressive joint damage in patients with RA involves the aberrant generation and activation of osteoclasts 141 . Osteoclastogenesis requires RANK, which can stimulate both the canonical and the non-canonical NF-κB pathways in osteoclast precursor cells 77 .…”

Section: Role In Inflammatory Diseasesmentioning

confidence: 99%

The non-canonical NF-κB pathway in immunity and inflammation

2017

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The nuclear factor-κB (NF-κB) family of transcription factors is activated by canonical and non-canonical signalling pathways, which differ in both signalling components and biological functions. Recent studies have revealed important roles for the non-canonical NF-κB pathway in regulating different aspects of immune functions. Defects in non-canonical NF-κB signalling are associated with severe immune deficiencies, whereas dysregulated activation of this pathway contributes to the pathogenesis of various autoimmune and inflammatory diseases. Here we review the signalling mechanisms and the biological function of the non-canonical NF-κB pathway. We also discuss recent progress in elucidating the molecular mechanisms regulating non-canonical NF-κB pathway activation, which may provide new opportunities for therapeutic strategies.

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Section: Role In Inflammatory Diseasesmentioning

confidence: 99%

The non-canonical NF-κB pathway in immunity and inflammation

2017

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“…Although many osteoinductive proteins have been proven effective in MSCs, the selection of BMP9 as a target protein needed exploration. BMP2, 4, 6, and 7, members of the TGF‐β superfamily, are potent osteoinductive growth factors that have been applied in clinical treatment . A previous study proposed a significantly stronger ability of BMP9 in inducing MSCs osteogenesis compared to other BMPs .…”

Section: Discussionmentioning

confidence: 99%

BMP9 promotes osteogenic differentiation of SMSCs by activating the JNK/Smad2/3 signaling pathway

Zheng

Chen

Zhang

et al. 2019

J of Cellular Biochemistry

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Synovial mesenchymal stem cells (SMSCs) with high proliferation and multi differentiation ability, and low immunogenicity have attracted research attention for their potential application in tissue engineering. Once their ability of osteogenesis is strengthened, it will be of practical value to apply the SMSCs in the field of bone regeneration. The current study aimed to investigate the osteogenic characteristics of SMSCs induced by bone morphogenetic protein 9 (BMP9) both in vitro and in vivo and to elucidate the mechanism underlying these characteristics. Specifically, different BMPs were assessed to determine the protein that would be the most favorable for stimulating osteogenic differentiation of SMSCs following their separation. The BMP9‐enhanced osteogenesis of SMSCs was fully investigated in vitro and in vivo, and the c‐Jun N‐terminal kinase (JNK)/Smad2/3 signaling pathway stimulated by BMP9 was further explored. Our data suggested that BMP9 could significantly promote gene and protein expression of runt‐related transcription factor 2, alkaline phosphatase, osteopontin, and osteocalcin, and SP600125, a JNK‐specific inhibitor, could effectively decrease this tendency. Similar results were also confirmed in rats with cranial defects. In conclusion, our study indicated that BMP9 promotes bone formation both in vitro and in vivo possibly by activating the JNK/Smad2/3 signaling pathway.

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“…Chronic joint inflammation causes dysregulated bone remodeling characterized by the promotion of bone destruction and inhibition of bone formation . Recent studies suggest repair of erosions in some RA patients treated with biologic agents such as TNF or IL‐6R inhibitors .…”

Section: Discussionmentioning

confidence: 99%

Multimodal [18F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNFα Transgenic Mice

Hayer

Zeilinger

Weiss

et al. 2019

Journal of Bone and Mineral Research

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In rheumatoid arthritis (RA), chronic joint inflammation leading to bone and cartilage damage is the major cause of functional impairment. Whereas reduction of synovitis and blockade of joint damage can be successfully achieved by disease modifying antirheumatic therapies, bone repair upon therapeutic interventions has only been rarely reported. The aim of this study was to use fluorodeoxyglucose ([18F]FDG) and [18F]fluoride µPET/CT imaging to monitor systemic inflammatory and destructive bone remodeling processes as well as potential bone repair in an established mouse model of chronic inflammatory, erosive polyarthritis. Therefore, human tumor necrosis factor transgenic (hTNFtg) mice were treated with infliximab, an anti‐TNF antibody, for 4 weeks. Before and after treatment period, mice received either [18F]FDG, for detecting inflammatory processes, or [18F]fluoride, for monitoring bone remodeling processes, for PET scans followed by CT scans. Standardized uptake values (SUVmean) were analyzed in various joints and histopathological signs of arthritis, joint damage, and repair were assessed. Longitudinal PET/CT scans revealed a significant decrease in [18F]FDG SUVs in affected joints demonstrating complete remission of inflammatory processes due to TNF blockade. In contrast, [18F]fluoride SUVs could not discriminate between different severities of bone damage in hTNFtg mice. Repeated in vivo CT images proved a structural reversal of preexisting bone erosions after anti‐TNF therapy. Accordingly, histological analysis showed complete resolution of synovial inflammation and healing of bone at sites of former bone erosion. We conclude that in vivo multimodal [18F]FDG µPET/CT imaging allows to quantify and monitor inflammation‐mediated bone damage and reveals not only reversal of synovitis but also bone repair upon TNF blockade in experimental arthritis. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

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Bone as a Target Organ in Rheumatic Disease: Impact on Osteoclasts and Osteoblasts

Cited by 83 publications

References 159 publications

The non-canonical NF-κB pathway in immunity and inflammation

The non-canonical NF-κB pathway in immunity and inflammation

BMP9 promotes osteogenic differentiation of SMSCs by activating the JNK/Smad2/3 signaling pathway

Multimodal [18F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNFα Transgenic Mice

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