Potential role of long non‐coding <scp>RNA <i>H19</i></scp> and <i>Neat1</i> in haemophilic arthropathy

Sarangi, Pratiksha; Senthilkumar, M; Kumar, Narendra; Senguttuvan, Senthilnathan; Vasudevan, Madavan; Jayandharan, Giridhara R.

doi:10.1111/jcmm.17770

Cited by 3 publications

(7 citation statements)

References 26 publications

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“…Our earlier data had demonstrated that Neat1 was substantially over expressed in the hemarthritic joints in a murine model of haemophilia A. 8 To investigate if downregulation of Neat1 is beneficial, we first cloned a previously reported shRNA sequence (48 bp) targeting mouse Neat1 21 in an Adeno‐associated virus (AAV) backbone containing a ubiquitous (U6) promoter (241 bp) (Figure S1A ). The shRNA against Neat1 used in this study was previously validated to be specifically targeting mouse Neat1 and hence, we did not use a scrambled shRNA as control for validation study.…”

Section: Resultsmentioning

confidence: 99%

“…Our earlier data had demonstrated that Neat1 was substantially over expressed in the hemarthritic joints in a murine model of haemophilia A 8 . To investigate if downregulation of Neat1 is beneficial, we first cloned a previously reported shRNA sequence (48 bp) targeting mouse Neat1 21 in an Adeno‐associated virus (AAV) backbone containing a ubiquitous (U6) promoter (241 bp) (Figure S1A).…”

Section: Resultsmentioning

confidence: 99%

“… 20 Previously, our group reported the upregulation of Neat1 in mouse model of chronic HA and its potential role in the regulation of MMPs. 8 Since HA is a joint disease that shares phenotypic manifestations noted in OA and RA, 49 we reasoned that downregulation of Neat1 may impact joint disease in haemophilia.…”

Section: Discussionmentioning

confidence: 99%

“… 7 In our previous study, we have also highlighted the emerging role of long non‐coding RNAs (lncRNAs) H19 and Neat1 in a mouse model of chronic HA. 8 The function of similar lncRNAs in other joint diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA), in terms of disease onset and advancement, has been extensively studied. 9 , 10 , 11 , 12 , 13 The dysregulation of lncRNAs, including Neat1 , H19 , Mir22hg and Malat1 , in collagen‐induced arthritis (CIA), OA and RA patients or in animal models, has also been reported.…”

Section: Introductionmentioning

confidence: 99%

“…We have demonstrated that overexpression of miR125a‐5p in tandem with F8 gene transfer using AAV vector diminished joint damage progression by downregulating the molecular mediators involved in the disease pathogenesis including MMP3, 9 and 13 7 . In our previous study, we have also highlighted the emerging role of long non‐coding RNAs (lncRNAs) H19 and Neat1 in a mouse model of chronic HA 8 . The function of similar lncRNAs in other joint diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA), in terms of disease onset and advancement, has been extensively studied 9–13 .…”

Section: Introductionmentioning

confidence: 99%

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AAV mediated repression of Neat1 lncRNA combined with F8 gene augmentation mitigates pathological mediators of joint disease in haemophilia

Sarangi,

Senthilkumar,

Amit

et al. 2024

J Cellular Molecular Medi

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Haemophilic arthropathy (HA), a common comorbidity in haemophilic patients leads to joint pain, deformity and reduced quality of life. We have recently demonstrated that a long non‐coding RNA, Neat1 as a primary regulator of matrix metalloproteinase (MMP) 3 and MMP13 activity, and its induction in the target joint has a deteriorating effect on articular cartilage. In the present study, we administered an Adeno‐associated virus (AAV) 5 vector carrying an short hairpin (sh)RNA to Neat1 via intra‐articular injection alone or in conjunction with systemic administration of a capsid‐modified AAV8 (K31Q) vector carrying F8 gene (F8‐BDD‐V3) to study its impact on HA. AAV8K31Q‐F8 vector administration at low dose, led to an increase in FVIII activity (16%–28%) in treated mice. We further observed a significant knockdown of Neat1 (~40 fold vs. untreated injured joint, p = 0.005) in joint tissue of treated mice and a downregulation of chondrodegenerative enzymes, MMP3, MMP13 and the inflammatory mediator‐ cPLA2, in mice receiving combination therapy. These data demonstrate that AAV mediated Neat1 knockdown in combination with F8 gene augmentation can potentially impact mediators of haemophilic joint disease.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%