Identification of miRNAs Associated With Gender Difference in Osteoarthritis Patients

NCT04851210 | Completed DMC

• 1 other identifier: 148/2021/Sper/IOR
• Study Type: observational
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The biological study involves the collection of samples from male and female patients (intraoperative waste tissue, blood and synovial fluid), suffering from mild and moderate-severe OA, who undergo endo or arthro-prosthesis surgery, or arthroplasty, for the identification and characterization of a panel of "gender-specific" miRNAs. MicroRNAs will be extracted from the samples (chondrocytes, synoviocytes, osteoblasts and plasma) and will be molecularly characterized in order to identify a panel of miRNAs differently expressed according to the gender and severity of OA. The lymphocyte and phenotypically and functionally characterized populations will be isolated from the corpuscular component and the synovial fluid, in order to evaluate a possible gender-specific difference in the progression of OA-dependent inflammation.

Conditions

Osteoarthritis

Keywords

miRNA; osteoarthritis; gender; biomarker

Outcome Measures

Primary Outcomes (1)

• Change assessment of OA 'gender-specific miRNA panel during time

  Identification and characterization of a 'gender-specific' miRNA panel related to disease progression in patients with mild OA (OA with Kellgren Lawrence-KL grade I and II) and moderate-severe (OA with greater or greater KL score equal to grade III). The miRNAs will be isolated from patients affected by OA who undergo endo- or arthro-prosthesis operations starting: 1) from cells isolated from waste tissues; and 2) from the plasma taken 24 hours before surgery, and subsequently at 72 hours and 1 month from this.

  Time points: 24 hours; 72 hours; 1 month

Secondary Outcomes (3)

• Functional role of OA 'gender-specific' miRNAs

  2 months

• Change assessment of OA 'gender-specific' inflammatory response during time

  Time points: 24 hours; 72 hours; 1 month

• OA 'gender-specific' miRNAs as biomarkers of osteointegration

  12 months

Interventions

No intervention OTHER

No intervention

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

A maximum number of n = 20 patients with clinical and radiological diagnosis of OA will be enrolled: n = 10 with OA defined as "moderate-severe" equivalent to the KL score greater than or equal to grade III (n = 5 males and n = 5 females); and n = 10 with OA defined as "mild" equivalent to the grade I and II KL score (n = 5 males and n = 5 females), who undergo endo or arthro-prosthesis surgery, or arthroscopy. All patients will be enrolled in the clinical trial only after having personally dated and signed the written informed consent.

You may qualify if:

• Patients of both sexes suffering from OA in hospital for the surgical treatment of OA (endo- or arthroplasty, or arthroscopy) with an interval of at least three months from any previous infiltrative treatment of any kind;
• Patients with a Kellgren and Lawrence (KL) \[Kohn 2016\] score greater than or equal to grade III will be enrolled in the 'Moderate-severe OA' group and those with grade I and II KL scores in the 'MIld OA' group;
• Patients able to provide the list of medications and supplements taken;
• Patients able to provide informed consent to treatment.

You may not qualify if:

• Patients who have undergone previous joint surgery or who have excessive joint deformity.
• Patients with recent trauma, osteonecrosis or OA induced by previous or current joint infection;
• Patients with metabolic pathologies;
• Patients with previous or current oncological pathologies;
• Women in a climacteric (date of last menstruation less than one year);
• Patients with severe cognitive deficits or psychiatric disorders;
• Autoimmune diseases (eg rheumatoid arthritis).

Sponsors & Collaborators

• Istituto Ortopedico Rizzoli: lead

Study Sites (1)

Dipartimento Rizzoli Sicilia - Istituto Ortopedico Rizzoli

Bagheria, Palermo, 90011, Italy

Location

Related Publications (15)

• Amodio N, Stamato MA, Gulla AM, Morelli E, Romeo E, Raimondi L, Pitari MR, Ferrandino I, Misso G, Caraglia M, Perrotta I, Neri A, Fulciniti M, Rolfo C, Anderson KC, Munshi NC, Tagliaferri P, Tassone P. Therapeutic Targeting of miR-29b/HDAC4 Epigenetic Loop in Multiple Myeloma. Mol Cancer Ther. 2016 Jun;15(6):1364-75. doi: 10.1158/1535-7163.MCT-15-0985. Epub 2016 May 18.

  PMID: 27196750 BACKGROUND

• Bellavia D, De Luca A, Carina V, Costa V, Raimondi L, Salamanna F, Alessandro R, Fini M, Giavaresi G. Deregulated miRNAs in bone health: Epigenetic roles in osteoporosis. Bone. 2019 May;122:52-75. doi: 10.1016/j.bone.2019.02.013. Epub 2019 Feb 14.

  PMID: 30772601 BACKGROUND

• Costa V, Lo Dico A, Rizzo A, Rajata F, Tripodi M, Alessandro R, Conigliaro A. MiR-675-5p supports hypoxia induced epithelial to mesenchymal transition in colon cancer cells. Oncotarget. 2017 Apr 11;8(15):24292-24302. doi: 10.18632/oncotarget.14464.

  PMID: 28061476 BACKGROUND

• Costa V, Raimondi L, Conigliaro A, Salamanna F, Carina V, De Luca A, Bellavia D, Alessandro R, Fini M, Giavaresi G. Hypoxia-inducible factor 1Alpha may regulate the commitment of mesenchymal stromal cells toward angio-osteogenesis by mirna-675-5P. Cytotherapy. 2017 Dec;19(12):1412-1425. doi: 10.1016/j.jcyt.2017.09.007. Epub 2017 Oct 27.

  PMID: 29111380 BACKGROUND

• Costa V, Carina V, Conigliaro A, Raimondi L, De Luca A, Bellavia D, Salamanna F, Setti S, Alessandro R, Fini M, Giavaresi G. miR-31-5p Is a LIPUS-Mechanosensitive MicroRNA that Targets HIF-1alpha Signaling and Cytoskeletal Proteins. Int J Mol Sci. 2019 Mar 28;20(7):1569. doi: 10.3390/ijms20071569.

  PMID: 30925808 BACKGROUND

• Costa V, Carina V, Raimondi L, De Luca A, Bellavia D, Conigliaro A, Salamanna F, Alessandro R, Fini M, Giavaresi G. MiR-33a Controls hMSCS Osteoblast Commitment Modulating the Yap/Taz Expression Through EGFR Signaling Regulation. Cells. 2019 Nov 22;8(12):1495. doi: 10.3390/cells8121495.

  PMID: 31771093 BACKGROUND

• Gago-Fuentes R, Fernandez-Puente P, Megias D, Carpintero-Fernandez P, Mateos J, Acea B, Fonseca E, Blanco FJ, Mayan MD. Proteomic Analysis of Connexin 43 Reveals Novel Interactors Related to Osteoarthritis. Mol Cell Proteomics. 2015 Jul;14(7):1831-45. doi: 10.1074/mcp.M115.050211. Epub 2015 Apr 22.

  PMID: 25903580 BACKGROUND

• Hunziker EB. Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage. 2002 Jun;10(6):432-63. doi: 10.1053/joca.2002.0801.

  PMID: 12056848 BACKGROUND

• Kohn MD, Sassoon AA, Fernando ND. Classifications in Brief: Kellgren-Lawrence Classification of Osteoarthritis. Clin Orthop Relat Res. 2016 Aug;474(8):1886-93. doi: 10.1007/s11999-016-4732-4. Epub 2016 Feb 12. No abstract available.

  PMID: 26872913 BACKGROUND

• Kriegova E, Manukyan G, Mikulkova Z, Gabcova G, Kudelka M, Gajdos P, Gallo J. Gender-related differences observed among immune cells in synovial fluid in knee osteoarthritis. Osteoarthritis Cartilage. 2018 Sep;26(9):1247-1256. doi: 10.1016/j.joca.2018.04.016. Epub 2018 May 19.

  PMID: 29753948 BACKGROUND

• Lo Dico A, Costa V, Martelli C, Diceglie C, Rajata F, Rizzo A, Mancone C, Tripodi M, Ottobrini L, Alessandro R, Conigliaro A. MiR675-5p Acts on HIF-1alpha to Sustain Hypoxic Responses: A New Therapeutic Strategy for Glioma. Theranostics. 2016 May 8;6(8):1105-18. doi: 10.7150/thno.14700. eCollection 2016.

  PMID: 27279905 BACKGROUND

• Lv ZT, Liang S, Huang XJ, Cheng P, Zhu WT, Chen AM. Association between ADAM12 Single-Nucleotide Polymorphisms and Knee Osteoarthritis: A Meta-Analysis. Biomed Res Int. 2017;2017:5398181. doi: 10.1155/2017/5398181. Epub 2017 Aug 8.

  PMID: 28929114 BACKGROUND

• Pan Q, O'Connor MI, Coutts RD, Hyzy SL, Olivares-Navarrete R, Schwartz Z, Boyan BD. Characterization of osteoarthritic human knees indicates potential sex differences. Biol Sex Differ. 2016 Jun 2;7:27. doi: 10.1186/s13293-016-0080-z. eCollection 2016.

  PMID: 27257472 BACKGROUND

• Pelletier JP, Martel-Pelletier J, Abramson SB. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum. 2001 Jun;44(6):1237-47. doi: 10.1002/1529-0131(200106)44:63.0.CO;2-F. No abstract available.

  PMID: 11407681 BACKGROUND

• Wang S, Wang H, Liu W, Wei B. Identification of Key Genes and Pathways Associated with Sex Differences in Osteoarthritis Based on Bioinformatics Analysis. Biomed Res Int. 2019 Dec 6;2019:3482751. doi: 10.1155/2019/3482751. eCollection 2019.

  PMID: 31886203 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood and synovial fluid specimen, surgical waste joint tissues (bone, sinovia, cartilage)

MeSH Terms

Conditions

Osteoarthritis; Coitus

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Sexual Behavior; Behavior

Study Officials

• Viviana Costa, B.Sc Ph.D

  IRCCS Istituto Ortopedico Rizzoli

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2021
• First Posted: April 20, 2021
• Study Start: March 21, 2022
• Primary Completion: July 31, 2024
• Study Completion: July 31, 2024
• Last Updated: September 23, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)