Biochemical and Biophysical Research Communications
Expression of PTHrP and its cognate receptor in the rheumatoid synovial microcirculation
Section snippets
Materials and methods
Immunohistochemical analysis of rheumatoid synovial tissue. Synovial tissue specimens obtained from patients with rheumatoid arthritis at the time of joint replacement surgery (n=5) were immediately fixed in 10% formalin and embedded in paraffin for immunohistochemical staining. Using previously described methods [5], tissues were processed for detection of PTHrP or the PTH/PTHrP receptor (PTH1R) using affinity purified rabbit polyclonal antibodies generated against either human PTHrP(34–53)
Expression of PTHrP in the rheumatoid synovial microcirculation
Endothelial cells (Fig. 1A) were the primary cellular site of vascular PTHrP expression in human rheumatoid synovial tissue (Table 1), as determined by immunohistochemical staining (Figs. 1B, E, G, and H). In all cases, specificity of PTHrP immunoreactivity was verified by the absence of staining that resulted on sequential sections treated with PTHrP antibody that had been preincubated with an excess of antigen. PTHrP-positive endothelial cells were present in all of the rheumatoid synovial
Discussion
This study provides a unique opportunity to examine the expression of PTHrP and its cognate receptor in the microcirculation of a human tissue that is undergoing active vascular remodeling. In the rheumatoid synovium, immunohistochemical studies identified endothelial cells as the primary site of vascular PTHrP expression, a finding further supported by the demonstration of PTHrP mRNA expression and protein secretion from cultured microvascular endothelial cells isolated from the rheumatoid
Acknowledgements
This work was supported by a grant from the Arthritis Foundation to J.L. Funk.
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2019, Molecular and Cellular EndocrinologyCitation Excerpt :Rian and collaborators (Rian et al., 1994) showed for the first time that PTHrP, but not the PTH/PTHrP receptor, is produced by human endothelial cells. As smooth muscle cells express PTH/PTHrP receptors (Funk et al., 2002), these investigators suggest that the hormone produced by endothelial cells may has a paracrine action on these muscle cells (Diamond et al., 2006), however, they cannot rule out an autocrine effect of PTHrP. Curiously, there are controversial results about the effects of PTHrP on angiogenesis.
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2012, Regulatory PeptidesCitation Excerpt :The inflammatory response in pancreatitis is accompanied by an increase in cytokine and chemokine levels. PTHrP exerts pro-inflammatory effects in the injured kidney, atherosclerosis and rheumatoid arthritis [13–17]. Here we measured the effects of PTHrP on IL-6 and ICAM-1 mRNA levels.
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Present address. Pfizer Global Research & Development, San Diego, USA.