Hypothalamic-pituitary-adrenal axis stress test in patients with early RA: role of corticotropin-releasing hormone promoter polymorphisms

Malysheva, O.; Wagner, Uta; Wahle, Matthias; Pierer, Matthias; Stalla, Günter; Baerwald, Christoph

doi:10.1136/ard.2011.151340

Cited by 5 publications

(4 citation statements)

References 10 publications

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“…In PTOA macrophages, compared to controls, collagen metabolism, myeloid differentiation regulation, neutrophil chemotaxis and glial cell apoptosis pathways were all enriched (Fig 3F). In RA macrophages on the other hand, response to corticotropin-releasing hormone (known to be pro-inflammatory and enriched in RA synovial fluid 38 ), Th1 differentiation, and cellular response to mercury were all perturbed (Fig 3G). Analysis of enriched pathways common between RA and PTOA macrophages yielded unsurprising results, including cytokine activity, white blood cell chemotaxis and migration, and signaling receptor activity (Fig 3H).…”

Section: Resultsmentioning

confidence: 99%

Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis

Knights,

Farrell,

Ellis

et al. 2023

Preprint

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ObjectiveSynovium is home to immune and stromal cell types that orchestrate inflammation following a joint injury; in particular, macrophages are central protagonists in this process. We sought to define the cellular and temporal dynamics of the synovial immune niche in a mouse model of post-traumatic osteoarthritis (PTOA), and to identify stromal-immune crosstalk mechanisms that coordinate macrophage function and phenotype.DesignWe induced PTOA in mice using a non-invasive tibial compression model of anterior cruciate ligament rupture (ACLR). Single cell RNA-seq and flow cytometry were used to assess immune cell populations in healthy (Sham) and injured (7d and 28d post-ACLR) synovium. Characterization of synovial macrophage polarization states was performed, alongside computational modeling of macrophage differentiation, as well as implicated transcriptional regulators and stromal-immune communication axes.ResultsImmune cell types are broadly represented in healthy synovium, but experience drastic expansion and speciation in PTOA, most notably in the macrophage portion. We identified several polarization states of macrophages in synovium following joint injury, underpinned by distinct transcriptomic signatures, and regulated in part by stromal-derived macrophage colony-stimulating factor signaling. The transcription factors Pu.1, Cebpα, Cebpβ, and Jun were predicted to control differentiation of systemically derived monocytes into pro-inflammatory synovial macrophages.ConclusionsWe defined different synovial macrophage subpopulations present in healthy and injured mouse synovium. Nuanced characterization of the distinct functions, origins, and disease kinetics of macrophage subtypes in PTOA will be critical for targeting these highly versatile cells for therapeutic purposes.

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Section: Resultsmentioning

confidence: 99%

Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis

Knights,

Farrell,

Ellis

et al. 2023

Preprint

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“…17,18 Corticotropin-releasing hormone encoded by the CRH gene, is a key integrator of stress responses, and, as such, CRH gene variation may contribute to individual differences in susceptibility to stress-related pathology. 19 CRH is the strongest known activator of the HPA axis, which has been functionally implicated in the regulation of many endocrine functions such as glucocorticoid release from the adrenal gland and associated endocrineimmune responses. 19 Stress due to relationship difficulties, bereavement in the family or forced migration in South Asians may have had effect on the hypothalamic-pituitary-adrenal axis where either the polymorphisms in the CRH gene or their expression may have played a part in RA occurrence.…”

Section: Discussionmentioning

confidence: 99%

Genetic analysis of CRHRA1 and CRHRA2 microsatellites and their association with rheumatoid arthritis in South Asian and Caucasian populations of the East Midlands, UK.

Ghelani

Steer²,

Fisher

et al. 2012

Rheumatol Rep

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“…The integrated cortisol response to hypoglycemia expressed as area under the curve was significantly lower in RA patients with the A1B1 allele than in RA patients with the A2B2 allele. Moreover, there was a significant difference in the molar ratio cortisol to ACTH between controls and RA patients underlining the dissociation of the pituitary and the adrenal gland in patients with RA (Malysheva et al, 2011).…”

Section: Integration Of Stress Hormones Cytokines and Neurotransmittersmentioning

confidence: 99%

The Pathogenetic Link Between Stress and Rheumatic Diseases

Malysheva¹,

Baerwald²

2012

Insights and Perspectives in Rheumatology

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Hypothalamic-pituitary-adrenal axis stress test in patients with early RA: role of corticotropin-releasing hormone promoter polymorphisms

Cited by 5 publications

References 10 publications

Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis

Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis

Genetic analysis of CRHRA1 and CRHRA2 microsatellites and their association with rheumatoid arthritis in South Asian and Caucasian populations of the East Midlands, UK.

The Pathogenetic Link Between Stress and Rheumatic Diseases

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