Parathyroid hormone-related peptide expression in rat collagen-induced arthritis

Godler, David E.; Stein, Alicia; Bakharevski, Olga; Lindsay, Mitchell; Ryan, P. F. J.

doi:10.1093/rheumatology/keh690

Cited by 7 publications

(8 citation statements)

References 49 publications

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“…Another strength is that this study confirms using multiple lines of evidence that measuring mRNA levels with qRT-PCR in PM related disorders requires an improved approach to the internal control methodology that is using at least two or three internal control genes determined to be stably expressed. One important limitation, and the direction for future studies, however, is that, a better approach would be through absolute quantification of mRNA using methods that do not rely on internal control normalization such as competitive PCR 42 or Droplet Digital PCR 43 , demonstrated to be effective for gene expression analysis in other settings. Other limitations include the relatively small sample size, the need to reproduce these findings in an independent cohort of PM females, and to explore contribution of GUS to the phenotype in PM males where FXTAS is more prevalent.…”

Section: Discussionmentioning

confidence: 99%

β-glucuronidase mRNA levels are correlated with gait and working memory in premutation females: understanding the role of FMR1 premutation alleles

Kraan

Cornish

Bui

et al. 2016

Sci Rep

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Fragile X tremor ataxia syndrome (FXTAS) is a late-onset disorder manifesting in a proportion of FMR1 premutation individuals (PM: 55-199 CGG triplet expansions). FXTAS is associated with elevated levels of FMR1 mRNA which are toxic. In this study, relationships between neurocognitive and intra-step gait variability measures with mRNA levels, measured in blood samples, were examined in 35 PM and 35 matched control females. The real-time PCR assays measured FMR1 mRNA, and previously used internal control genes: β-Glucuronidase (GUS), Succinate Dehydrogenase 1 (SDHA) and Eukaryotic Translation Initiation Factor 4A (EI4A2). Although there was significant correlation of gait variability with FMR1 mRNA levels (p = 0.004) when normalized to GUS (FMR1/GUS), this was lost when FMR1 was normalized to SDHA and EI4A2 (2IC). In contrast, GUS mRNA level normalized to 2IC showed a strong correlation with gait variability measures (p < 0.007), working memory (p = 0.001) and verbal intelligence scores (p = 0.008). PM specific changes in GUS mRNA were not mediated by FMR1 mRNA. These results raise interest in the role of GUS in PM related disorders and emphasise the importance of using appropriate internal control genes, which have no significant association with PM phenotype, to normalize FMR1 mRNA levels.

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Section: Discussionmentioning

confidence: 99%

β-glucuronidase mRNA levels are correlated with gait and working memory in premutation females: understanding the role of FMR1 premutation alleles

Kraan

Cornish

Bui

et al. 2016

Sci Rep

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“…In the rat CIA model, PTHrP levels increased in joint synovium 10 days following onset of the disease and peaked at 20 days postdisease onset. Expression of PTHrP was localized to neutrophils, cells of the osteoblast lineage, and mononucleated and multinucleated cells of the monocyte–macrophage lineage (likely to be osteoclasts) (169). The contribution of PTHrP to arthritis‐induced bone loss was demonstrated in the rat streptococcal cell wall (SCW)‐induced model.…”

Section: Pthrpmentioning

confidence: 99%

Rheumatic diseases: the effects of inflammation on bone

Walsh

Crotti

Goldring

et al. 2005

Immunological Reviews

349

262

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Rheumatoid arthritis, juvenile idiopathic arthritis, the seronegative spondyloarthropathies including psoriatic arthritis, and systemic lupus erythematosus are all examples of rheumatic diseases in which inflammation is associated with skeletal pathology. Although some of the mechanisms of skeletal remodeling are shared among these diseases, each disease has a unique impact on articular bone or on the axial or appendicular skeleton. Studies in human disease and in animal models of arthritis have identified the osteoclast as the predominant cell type mediating bone loss in arthritis. Many of the cytokines and growth factors implicated in the inflammatory processes in rheumatic diseases have also been demonstrated to impact osteoclast differentiation and function either directly, by acting on cells of the osteoclast-lineage, or indirectly, by acting on other cell types to modulate expression of the key osteoclastogenic factor receptor activator of nuclear factor (NF) kappaB ligand (RANKL) and/or its inhibitor osteoprotegerin (OPG). Further elucidation of the mechanisms responsible for inflammation-induced bone loss will potentially lead to the identification of novel therapeutic strategies for the prevention of bone loss in these diseases. In this review, we provide an overview of the cell types, inflammatory mediators, and mechanisms that are implicated in bone loss and new bone formation in inflammatory joint diseases.

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“…PTHrP is normally expressed by articular chondrocytes in low amounts and is increased following application of mechanical load [32, 33] or in OA [34]. It has been established recently that PTHrP is required for articular cartilage maintenance given that Gdf5-Cre -targeted knockdown of PTHrP in mid-region articular chondrocytes leads to accelerated development of posttraumatic OA in the mouse [35].…”

Section: Introductionmentioning

confidence: 99%

Teriparatide as a Chondroregenerative Therapy for Injury-Induced Osteoarthritis

et al. 2011

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There is no disease-modifying therapy for osteoarthritis, a degenerative joint disease that is projected to afflict more than 67 million individuals in the US alone by 2030. As disease pathogenesis is associated with inappropriate articular chondrocyte maturation resembling that seen during normal endochondral ossification, pathways that govern the maturation of these cells are candidate therapeutic targets. It is well established that parathyroid hormone (PTH) induces matrix synthesis and suppresses maturation of chondrocytes via the type 1 PTH receptor. We have found that the PTH receptor is up-regulated in articular chondrocytes following meniscal injury and during osteoarthritis in humans and in a mouse model of injury-induced knee osteoarthritis. Thus, we hypothesized that recombinant human PTH(1–34) (teriparatide) would inhibit aberrant chondrocyte maturation and associated articular cartilage degeneration. To test this, we administered systemic teriparatide (Forteo), an FDA-approved treatment for osteoporosis, either immediately after or 8 weeks after meniscal/ligamentous injury in mice. Knee joints were harvested at 4, 8, or 12 weeks post-injury to examine the effects of teriparatide on cartilage degeneration and articular chondrocyte maturation. Confirming successful systemic delivery of the drug, micro-computed tomography revealed increased bone volume within joints from teriparatide-treated mice compared to saline-treated controls. Immediate systemic administration of teriparatide increased proteoglycan content and inhibited articular cartilage degeneration, whereas delayed treatment beginning 8 weeks post-injury induced a regenerative effect. The chondro-protective and chondro-regenerative effects of teriparatide correlated with decreased levels of type × collagen, Runx2, matrix metalloproteinase-13 and the c-terminal aggrecan cleavage product NITEGE. These preclinical findings provide proof-of-concept that teriparatide (Forteo) may be useful for decelerating cartilage degeneration and inducing matrix regeneration in osteoarthritis patients.

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Parathyroid hormone-related peptide expression in rat collagen-induced arthritis

Abstract: Changes in ILN and PLN PTHrP mRNA expression suggest that elevated levels of the cytokine are associated with aggravation of the inflammatory immune response. Changes in PTHrP in DIP joints indicate its involvement in late rather than early pathogenic events in CIA joints.

Cited by 7 publications

References 49 publications

β-glucuronidase mRNA levels are correlated with gait and working memory in premutation females: understanding the role of FMR1 premutation alleles

β-glucuronidase mRNA levels are correlated with gait and working memory in premutation females: understanding the role of FMR1 premutation alleles

Rheumatic diseases: the effects of inflammation on bone

Teriparatide as a Chondroregenerative Therapy for Injury-Induced Osteoarthritis

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