The multifaced role of HtrA1 in the development of joint and skeletal disorders

Tossetta, Giovanni; Fantone, Sonia; Licini, Caterina; Marzioni, Daniela; Mattioli‐Belmonte, Monica

doi:10.1016/j.bone.2022.116350

Cited by 40 publications

(30 citation statements)

References 90 publications

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“…Natural compounds from plants, fungi, and marine organisms have been widely used worldwide as dietary supplements or natural drugs in traditional medicine. These compounds show numerous beneficial effects, such as antioxidant, anti-inflammatory, and anti-cancer effects [ 3 , 14 , 92 , 93 , 94 , 95 , 96 ]. Phenethyl isothiocyanate (PEITC) is an isothiocyanate present in cruciferous vegetables that has shown antioxidant and anticancer activities [ 97 , 98 ].…”

Section: Role Of Metformin In Cotreatment With Sb203580 or Phenethyl ...mentioning

confidence: 99%

Metformin Improves Ovarian Cancer Sensitivity to Paclitaxel and Platinum-Based Drugs: A Review of In Vitro Findings

Tossetta

2022

IJMS

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Ovarian cancer is one of the most dangerous gynecologic cancers worldwide, showing a high fatality rate and recurrence due to diagnosis at an advanced stage of the disease and the occurrence of chemoresistance, which weakens the therapeutic effects of the chemotherapeutic treatments. In fact, although paclitaxel and platinum-based drugs (carboplatin or cisplatin) are widely used alone or in combination to treat ovarian cancer, the occurrence of chemoresistance significantly reduces the effects of these drugs. Metformin is a hypoglycemic agent that is commonly used for the treatment of type 2 diabetes mellitus and non-alcoholic fatty liver disease. However, this drug also shows anti-tumor activity, reducing cancer risk and chemoresistance. This review analyzes the current literature regarding the role of metformin in ovarian cancer and investigates what is currently known about its effects in reducing paclitaxel and platinum resistance to restore sensitivity to these drugs.

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Section: Role Of Metformin In Cotreatment With Sb203580 or Phenethyl ...mentioning

confidence: 99%

Metformin Improves Ovarian Cancer Sensitivity to Paclitaxel and Platinum-Based Drugs: A Review of In Vitro Findings

Tossetta

2022

IJMS

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“…Previous studies using the same OA model have shown an increase in the SF concentration of PGE2 and glycosaminoglycans in the OA joints shortly after OA induction (within the first two weeks) and an increase in the matrix degradation products CPII, CS846 and C1,2C only toward the end of the 70-day study period (59). Prior to FDR correction ANOVA identified 39 DE proteins with respect to group (control and OA), including: Spondin-1 (p = 0.005), HtrA1 serine endopeptidase (p = 0.02), and serotransferrin (p = 0.01), all of which have been previously implicated in OA pathogenesis (60)(61)(62). Thus, whilst we cannot be certain there appears to be an effect on the EV proteome following OA induction that would require further exploration with additional animal studies.…”

Section: Figurementioning

confidence: 99%

Temporal extracellular vesicle protein changes following intraarticular treatment with integrin α10β1-selected mesenchymal stem cells in equine osteoarthritis

Clarke

Johnson²,

Gutierrez³

et al. 2022

Front. Vet. Sci.

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IntroductionEquine osteoarthritis (OA) is a heterogeneous, degenerative disease of the musculoskeletal system with multifactorial causation, characterized by a joint metabolic imbalance. Extracellular vesicles are nanoparticles involved in intracellular communication. Mesenchymal stem cell (MSC) therapy is a form of regenerative medicine that utilizes their properties to repair damaged tissues. Despite its wide use in veterinary practice, the exact mechanism of action of MSCs is not fully understood. The aim of this study was to determine the synovial fluid extracellular vesicle protein cargo following integrin α10β1-selected mesenchymal stem cell (integrin α10-MSC) treatment in an experimental model of equine osteoarthritis with longitudinal sampling.MethodsAdipose tissue derived, integrin α10-MSCs were injected intraarticularly in six horses 18 days after experimental induction of OA. Synovial fluid samples were collected at day 0, 18, 21, 28, 35, and 70. Synovial fluid was processed and extracellular vesicles were isolated and characterized. Extracellular vesicle cargo was then analyzed using data independent acquisition mass spectrometry proteomics.ResultsA total of 442 proteins were identified across all samples, with 48 proteins differentially expressed (FDR ≤ 0.05) between sham-operated control joint without MSC treatment and OA joint treated with MSCs. The most significant pathways following functional enrichment analysis of the differentially abundant protein dataset were serine endopeptidase activity (p = 0.023), complement activation (classical pathway) (p = 0.023), and collagen containing extracellular matrix (p = 0.034). Due to the lack of an OA group without MSC treatment, findings cannot be directly correlated to only MSCs.DiscussionTo date this is the first study to quantify the global extracellular vesicle proteome in synovial fluid following MSC treatment of osteoarthritis. Changes in the proteome of the synovial fluid-derived EVs following MSC injection suggest EVs may play a role in mediating the effect of cell therapy through altered joint homeostasis. This is an important step toward understanding the potential therapeutic mechanisms of MSC therapy, ultimately enabling the improvement of therapeutic efficacy.

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“…The severity of OA phenotype is also a limitation, as the model has been shown to produce a post-traumatic OA phenotype with respect to clinical parameters, but molecularly there were no significant proteins identified between control and OA. Prior to FDR correction ANOVA identified 39 DE proteins with respect to group (control and OA), including: Spondin-1 (p=0.005), HtrA1 serine endopeptidase (p=0.02), and serotransferrin (p=0.01), all of which have been previously implicated in OA pathogenesis (42)(43)(44). Thus whilst we cannot be certain there appears to be an effect on the EV proteome following OA induction that would requ further validation.…”

Section: Discussionmentioning

confidence: 93%

Temporal Extracellular Vesicle Protein Changes following Intraarticular Treatment with Integrin α10β1-selected Mesenchymal Stem Cells in Equine Osteoarthritis

Clarke

Johnson

Gutierrez

et al. 2022

Preprint

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Equine osteoarthritis is a heterogeneous, degenerative disease of the musculoskeletal system with multifactorial causation, characterised by a joint metabolic imbalance. Extracellular vesicles are nanoparticles involved in intracellular communication. Mesenchymal stem cell (MSC) therapy is a form of regenerative medicine that utilises their properties to repair damaged tissues. Despite its wide use in veterinary practice, the exact mechanism of action of MSCs is not fully understood. The aim of this study was to determine the synovial fluid extracellular vesicle protein cargo following integrin aplha 10 beta 1-selected mesenchymal stem cell treatment in an experimental model of equine osteoarthritis with longitudinal sampling. Adipose tissue derived, integrin aplha 10 beta 1-MSCs were injected into the osteoarthritis afflicted joint after 18 days post surgery. Sixty-nine synovial fluid samples were collected via aseptic arthrocentesis at day 0, 18, 21, 28, 35, and 70. Synovial fluid was hyaluronidase treated and extracellular vesicles isolated using differential ultracentrifugation. Extracellular vesicles were characterised using the Exoview human tetraspanin chip. Extracellular vesicle concentration, surface marker identification, fluorescent microscopy and tetraspanin colocalization analysis was undertaken, in conjunction with nanoparticle tracking analysis. For proteomics, extracellular vesicle pellets were suspended in urea lysis buffer. Samples were reduced, alkylated and digested on SP3 beads with trypsin/LysC. A data independent acquisition mode was utilised for nano liquid chromatography tandem mass spectrometry analysis on a Triple TOF 6600 mass spectrometer. A total of 442 proteins were identified across all samples, with 48 proteins differentially expressed (FDR≤ 0.05) between control and osteoarthritis treated with MSCs. The most significant pathways following functional enrichment analysis of the differentially abundant protein dataset were serine endopeptidase activity (p=0.023), complement activation (classical pathway) (p=0.023), and collagen containing extracellular matrix (p=0.034). To date this is the first study to quantify the global extracellular vesicle proteome in synovial fluid following MSC treatment of osteoarthritis. Changes in the proteome of the synovial fluid-derived EVs following MSC injection suggest EVs may play a role in mediating the effect of cell therapy through altered joint homeostasis and an improved phenotype.

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The multifaced role of HtrA1 in the development of joint and skeletal disorders

Cited by 40 publications

References 90 publications

Metformin Improves Ovarian Cancer Sensitivity to Paclitaxel and Platinum-Based Drugs: A Review of In Vitro Findings

Metformin Improves Ovarian Cancer Sensitivity to Paclitaxel and Platinum-Based Drugs: A Review of In Vitro Findings

Temporal extracellular vesicle protein changes following intraarticular treatment with integrin α10β1-selected mesenchymal stem cells in equine osteoarthritis

Temporal Extracellular Vesicle Protein Changes following Intraarticular Treatment with Integrin α10β1-selected Mesenchymal Stem Cells in Equine Osteoarthritis

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