Dataset Information

The Bone Marrow Edema Links to an Osteoclastic Environment and Precedes Synovitis During the Development of Collagen Induced Arthritis.

ABSTRACT: Objectives: To determine the relationship between bone marrow edema (BME), synovitis, and bone erosion longitudinally using a collagen induced arthritis mice (CIA) model and to explore the potential pathogenic role of BME in bone erosion. Methods: CIA was induced in DBA/1J mice. BME and corresponding clinical symptoms of arthritis and synovitis during the different time points of CIA development were assayed by magnetic resonance imaging (MRI), arthritis sore, and histologic analyses. The expression of osteoclasts (OCs), OCs-related cytokines, and immune cells in bone marrow were determined by flow cytometry, immunohistochemistry, immunofluorescence staining, and real-time PCR. The OCs formation was estimated using in vitro assays. Results: MRI detected BME could emerge at day 25 in 70% mice after the first immunization (n = 10), when there were not any arthritic symptoms, histological or MRI synovitis. At day 28, BME occurred in 90% mice whereas the arthritic symptom and histological synovitis were only presented in 30 and 20% CIA mice at that time (n = 10). The emergence of BME was associated with an increased bone marrow OCs number and an altered distribution of OCs adherent to subchondral bone surface, which resulted in increased subchondral erosion and decreased trabecular bone number during the CIA process. Obvious marrow environment changes were identified after BME emergence, consisting of multiple OCs related signals, including highly expressed RANKL, increased proinflammatory cytokines and chemokines, and highly activated T cells and monocytes. Conclusions: BME reflects a unique marrow "osteoclastic environment," preceding the arthritic symptoms and synovitis during the development of CIA.

SUBMITTER: Wang F

PROVIDER: S-EPMC6491763 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Bone Marrow Edema Links to an Osteoclastic Environment and Precedes Synovitis During the Development of Collagen Induced Arthritis.

Wang Fang F Luo Aishu A Xuan Wenhua W Qi Liang L Wu Qing Q Gan Ke K Zhang Qiande Q Zhang Miaojia M Tan Wenfeng W

Frontiers in immunology 20190424

<b>Objectives:</b> To determine the relationship between bone marrow edema (BME), synovitis, and bone erosion longitudinally using a collagen induced arthritis mice (CIA) model and to explore the potential pathogenic role of BME in bone erosion. <b>Methods:</b> CIA was induced in DBA/1J mice. BME and corresponding clinical symptoms of arthritis and synovitis during the different time points of CIA development were assayed by magnetic resonance imaging (MRI), arthritis sore, and histologic analys ...[more]

PMID: 31068949

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Project description:Osteoarthritis (OA) may result from impaired ability of synovial macrophages to resolve joint inflammation. Increasing macrophage counts in inflamed joints through injection with bone marrow mononuclear cells (BMNC) induces lasting resolution of synovial inflammation. To uncover mechanisms by which BMNC may affect resolution, in this study, differential transcriptional signatures of BMNC in response to normal (SF) and inflamed synovial fluid (ISF) were analyzed. We demonstrate the temporal behavior of co-expressed gene networks associated with traits from related in vivo and in vitro studies. We also identified activated and inhibited signaling pathways and upstream regulators, further determining their protein expression in the synovium of inflamed joints treated with BMNC or DPBS controls. BMNC responded to ISF with an early pro-inflammatory response characterized by a short spike in the expression of a NF-ƙB- and mitogen-related gene network. This response was associated with sustained increased expression of two gene networks comprising known drivers of resolution (IL-10, IGF-1, PPARG, isoprenoid biosynthesis). These networks were common to SF and ISF, but more highly expressed in ISF. Most highly activated pathways in ISF included the mevalonate pathway and PPAR-γ signaling, with pro-resolving functional annotations that improve mitochondrial metabolism and deactivate NF-ƙB signaling. Lower expression of mevalonate kinase and phospho-PPARγ in synovium from inflamed joints treated with BMNC, and equivalent IL-1β staining between BMNC- and DPBS-treated joints, associates with accomplished resolution in BMNC-treated joints and emphasize the intricate balance of pro- and anti-inflammatory mechanisms required for resolution. Combined, our data suggest that BMNC-mediated resolution is characterized by constitutively expressed homeostatic mechanisms, whose expression are enhanced following inflammatory stimulus. These mechanisms translate into macrophage proliferation optimizing their capacity to counteract inflammatory damage and improving their general and mitochondrial metabolism to endure oxidative stress while driving tissue repair. Such effect is largely achieved through the synthesis of several lipids that mediate recovery of homeostasis. Our study reveals candidate mechanisms by which BMNC provide lasting improvement in patients with OA and suggests further investigation on the effects of PPAR-γ signaling enhancement for the treatment of arthritic conditions.

Project description:synovial macrophages through joint injection with bone marrow mononuclear cells (BMNC) induces lasting synovial inflammation resolution. To uncover mechanisms by which BMNC may affect resolution, in this study, differential transcriptional signatures of BMNC in response to normal (SF) and inflamed synovial fluid (ISF) were analyzed. We demonstrate the temporal behavior of co-expressed gene networks associated with traits from our previous in vivo and in vitro studies. We also identified activated and inhibited signaling pathways and upstream regulators, further determining their protein expression in the synovium of inflamed joints treated with BMNC or DPBS controls. BMNC responded to ISF with an early pro-inflammatory response characterized by a short spike in the expression of a NF-ƙB- and mitogen-related gene network. This response was associated with sustained increased expression of another gene network comprising known drivers of resolution (IL-10, IGF-1, PPARG, isoprenoid biosynthesis). This network was common to SF and ISF, but more highly expressed in ISF and. Similarly, most highly activated pathways in ISF included the super pathway of cholesterol biosynthesis and PPAR‐γ signaling, with pro‐resolving functional annotations that improve mitochondrial metabolism and deactivate NF-ƙB signaling. Higher expression of the PPAR‐γ c0‐activator 1-ɑ in synovium from inflamed joints treated with BMNC, and equivalent IL‐1β staining between BMNC‐ and DPBS‐treated joints, emphasize the intricate balance of pro- and anti-inflammatory mechanisms required for resolution. Combined, our data suggest that BMNC-mediated resolution is characterized by constitutively expressed homeostatic mechanisms, whose expression are enhanced following tissue damage. These mechanisms translate into macrophage proliferation optimizing their capacity to counteract inflammatory damage and improving their general and mitochondrial metabolism to endure oxidative stress while driving tissue repair. Such effect is largely achieved through the synthesis of several lipids that mediate recovery of homeostasis. Our study reveals candidate mechanisms by which BMNC provide lasting improvement in patients with OA and suggests further investigation on the effects of PPAR‐γ signaling enhancement for the treatment of arthritic conditions.

Dataset Information

The Bone Marrow Edema Links to an Osteoclastic Environment and Precedes Synovitis During the Development of Collagen Induced Arthritis.

Publications

The Bone Marrow Edema Links to an Osteoclastic Environment and Precedes Synovitis During the Development of Collagen Induced Arthritis.

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