Curcumin as an effective suppressor of miRNA expression in patients with knee osteoarthritis

Document Type : Short communication

Authors

1 Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran

2 Rheumatic Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3 Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Epidemiology, Social Determinants of Health Research Center, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran

5 Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

6 Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

Abstract

Objective: Osteoarthritis is the most common disease in the group of joint diseases, and its incidence is directly related to aging. Given the anti-inflammatory effects of curcumin as an active ingredient of turmeric, we aimed to investigate the effects of this compound in a new curcumin nanomicelle formula named SinaCurcumin® on the expression of microRNAs (miRNAs) involved in immune responses of patients with osteoarthritis.
Materials and Methods: We divided 30 patients with osteoarthritis into two groups namely, nano curcumin-receiving (15 patients) and placebo-receiving (15 patients) and we studied them for 3 months. The Iranian Registry of Clinical Trials (IRCT) approved our study with the IRCT registry No. IRCT20151028024760N4. We evaluated the rates of the expression of microRNAs 146, 155, 16, and 138 employing SYBR Green Real-Time PCR method.
Results: The expression of miRNAs 155, 138, and 16 revealed a significant reduction in the curcumin-receiving group (p=0.002, p=0.024 and p=0.0001 respectively).
Conclusion: Our research data indicated that the consumption of curcumin in patients with osteoarthritis could affect the immune system partially via altering the expression of microRNAs and cytokines.

Keywords


Afshar S, Warden E, Manochehri H, Saidijam
M. 2019. Application of artificial neural
network in miRNA biomarker selection and
precise diagnosis of colorectal cancer. Iran
Biomed J, 23: 175-183.
Amalraj A, Varma K, Jacob J, Divya C,
Kunnumakkara A, Stohs S ,Gopi S. 2017.
A novel highly bioavailable curcumin
formulation improves symptoms and
diagnostic indicators in rheumatoid arthritis
patients: A randomized, double-blind,
placebo-controlled, two-dose, three-arm,
and parallel-group study. J Med Food, 20:
1022-1030.
Atabaki M, Shariati-Sarabi Z, TavakkolAfshari J, Mohammadi M. 2020.
Significant immunomodulatory properties
of curcumin in patients with osteoarthritis;
a successful clinical trial in Iran. Int
Immunopharmacol, 85: 106607.
Belcaro G, Cesarone M, Dugall M, Pellegrini
L, Ledda A, Grossi M, Togni S,
Appendino G. 2010. Product-evaluation
registry of Meriva(R), a curcuminphosphatidylcholine complex, for the
complementary management of
osteoarthritis. Panminerva Med, 52: 55-62.
Chen C, Zhou Y, Wang J, Yan Y, Peng L, Qiu
W. 2018. Dysregulated microRNA
involvement in multiple sclerosis by
induction of T helper 17 cell
differentiation. Front Immunol, 9: 1256.
Gol-Ara M, Jadidi-Niaragh F, Sadria R, Azizi
G, Mirshafiey A. 2012. The role of
different subsets of regulatory T cells in
immunopathogenesis of rheumatoid
arthritis. Arthritis, 2012: 805875.
Curcumin effects on MicroRNA gene expression in OA patients
AJP, Vol. 12, No. 4, Jul-Aug 2022 355
Han Z, Zhang J, Zhang K, Zhao Y. 2020.
Curcumin inhibits cell viability, migration,
and invasion of thymic carcinoma cells via
downregulation of microRNA-27a.
Phytother Res, 34: 1629-1637.
Hanada M, Takahashi M, Furuhashi H,
Koyama H, Matsuyama Y. 2016. Elevated
erythrocyte sedimentation rate and highsensitivity C-reactive protein in
osteoarthritis of the knee: relationship with
clinical findings and radiographic severity.
Ann Clin Biochem, 53: 548-553.
Haseeb A, Haqqi T. 2013.
Immunopathogenesis of osteoarthritis. Clin
Immunol, 146: 185-196.
Hsu Y, Chang S, Lin Y, Yang. 2017.
MicroRNA-146a alleviates experimental
autoimmune anterior uveitis in the eyes of
Lewis rats. Mediators Inflamm, 2017:
9601349.
King J, Ung N, Paing M, Contreras J, Alberti
M, Fernando T, Zhang K, Pellegrini M,
Rao D. 2016. Regulation of marginal zone
B-cell differentiation by microRNA-146a.
Front Immunol, 7: 670.
Kopanska M, Szala D, Czech J, Gablo N,
Gargasz K, Trzeciak M, Zawlik I, Snela S.
2017. MiRNA expression in the cartilage of
patients with osteoarthritis. J Orthop Surg
Res, 12: 51.
Li B, Wang X, Choi I, Wang Y, Liu S, Pham
A, Moon H, Smith D, Rao D, Boldin M,
Yang L. 2017. miR-146a modulates
autoreactive Th17 cell differentiation and
regulates organ-specific autoimmunity. J
Clin Invest, 127: 3702-3716.
Li G, Bu J, Zhu Y, Xiao X, Liang Z, Zhang R
2015. Curcumin improves bone
microarchitecture in glucocorticoid-induced
secondary osteoporosis mice through the
activation of microRNA-365 via regulating
MMP-9. Int J Clin Exp Pathol, 8: 15684-
15695.
Li L, Jia J, Liu X, Yang S, Ye S, Yang W,
Zhang Y. 2015. MicroRNA-16-5p Controls
Development of Osteoarthritis by Targeting
SMAD3 in Chondrocytes. Curr Pharm Des,
21: 5160-5167.
Li S, Wan J, Anderson W, Sun H, Zhang H,
Peng X, Yu Z, Wang T, Yan X, Smith W.
2016. Downregulation of IL-10 secretion
by Treg cells in osteoarthritis is associated
with a reduction in Tim-3 expression.
Biomed Pharmacother, 79: 159-165.
Li Y, Luo W, Zhu S, Lei G. 2017. T cells in
osteoarthritis: Alterations and beyond.
Front Immunol, 8: 356.
Luckheeram R, Zhou R, Verma A, Xia B.
2012. CD4(+)T cells: differentiation and
functions. Clin Dev Immunol, 2012:
925135.
Lurati A, Laria A, Gatti A, Brando B,
Scarpellini M. 2015. Different T cells'
distribution and activation degree of Th17
CD4+ cells in peripheral blood in patients
with osteoarthritis, rheumatoid arthritis, and
healthy donors: preliminary results of the
MAGENTA CLICAO study. Open Access
Rheumatol, 7: 63-68.
Ma F, Liu F, Ding L, You M, Yue H, Zhou Y,
Hou Y. 2017. Anti-inflammatory effects of
curcumin are associated with down
regulating microRNA-155 in LPS-treated
macrophages and mice. Pharm Biol, 55:
1263-1273.
Ma L, Xue H, Wang F, Shu C, Zhang. 2015.
MicroRNA-155 may be involved in the
pathogenesis of atopic dermatitis by
modulating the differentiation and function
of T helper type 17 (Th17) cells. Clin Exp
Immunol, 181: 142-149.
Mehana E, Khafaga A, El-Blehi S. 2019. The
role of matrix metalloproteinases in
osteoarthritis pathogenesis: An updated
review. Life Sci, 234: 116786.
Merkenschlager M. 2014. Jarid2 links
MicroRNA and chromatin in Th17 cells.
Immunity, 40: 855-856.
Momtazi A, Shahabipour F, Khatibi S,
Johnston T, Pirro M, Sahebkar A. 2016.
Curcumin as a microRNA regulator in
cancer: A review. Rev Physiol Biochem
Pharmacol, 171: 1-38.
Nakagawa Y, Mukai S, Yamada S, Matsuoka
M, Tarumi E, Hashimoto T, Tamura C,
Imaizumi A, Nishihira J, Nakamura T.
2014. Short-term effects of highlybioavailable curcumin for treating knee
osteoarthritis: a randomized, double-blind,
placebo-controlled prospective study. J
Orthop Sci, 19: 933-939.
Nugent M. 2016. MicroRNAs: exploring new
horizons in osteoarthritis. Osteoarthritis
Cartilage, 24: 573-580.
Onakpoya I, Spencer E, Perera R, Heneghan
C. 2017. Effectiveness of curcuminoids in
the treatment of knee osteoarthritis: a
systematic review and meta-analysis of
Atabaki et al.
AJP, Vol. 12, No. 4, Jul-Aug 2022 356
randomized clinical trials. Int J Rheum Dis,
20: 420-433.
Panagopoulos P, Lambrou G. 2018. The
Involvement of microRNAs in
osteoarthritis and recent developments: A
narrative review. Mediterr J Rheumatol, 29:
67-79.
Panahi Y, Hosseini M, Khalili N, Naimi E,
Majeed M, Sahebkar A. 2015. Antioxidant
and anti-inflammatory effects of
curcuminoid-piperine combination in
subjects with metabolic syndrome: A
randomized controlled trial and an updated
meta-analysis. Clin Nutr, 34: 1101-1108.
Phuah N, Nagoor N. 2014. Regulation of
microRNAs by natural agents: new
strategies in cancer therapies. Biomed Res
Int, 2014: 804510.
Rahimnia A, Panahi Y, Alishiri G, Sharafi M,
Sahebkar A. 2015. Impact of
supplementation with curcuminoids on
systemic inflammation in patients with
knee osteoarthritis: Findings from a
randomized double-blind placebocontrolled trial. Drug Res (Stuttg), 65: 521-
525.
Sakkas L, Platsoucas C. 2007. The role of T
cells in the pathogenesis of osteoarthritis.
Arthritis Rheum, 56: 409-424.
Seidl C, Martinez-Sanchez A, Murphy C.
2016. Derepression of microRNA-138
contributes to loss of the human articular
chondrocyte phenotype. Arthritis
Rheumatol, 68: 398-409.
Shep D, Khanwelkar C, Gade P, Karad S.
2019. A randomized controlled trial of
curcumin and diclofenac combination in
knee osteoarthritis. Int J Curr Pharm
Res, 11: 111-114.
Shep D, Khanwelkar C, Gade P, Karad S.
2019. Safety and efficacy of curcumin
versus diclofenac in knee osteoarthritis: a
randomized open-label parallel-arm study.
Trials, 20: 214.
Sondag G, Haqqi T. 2016. The role of
microRNAs and their targets in
osteoarthritis. Curr Rheumatol Rep, 18: 56.
Su L, Huang F, Jia H, Liu Y, Xu W. 2017.
Role of microRNA-155 in rheumatoid
arthritis. Int J Rheum Dis, 20: 1631-1637.
Testa U, Pelosi E, Castelli G, Labbaye C.
2017. miR-146 and miR-155: Two key
modulators of immune response and tumor
development. Noncoding RNA, 3: 22.
Wu Y, Liu W, Xue B, Zhang L, Liu X, Liu B,
Wang Y, Cai Y, Duan R. 2016.
Upregulated expression of microRNA-16
correlates with Th17/Treg cell imbalance in
patients with rheumatoid arthritis. DNA
Cell Biol, 35: 853-860.
Zhang A, Wang K, Zhou C, Gan Z, Ma D, Ye
P, Sun Y, Wu J, Huang X, Ren L, Deng P,
Wu C, Yue Z, Ding X, Chen J, Xia J. 2017.
Knockout of microRNA-155 ameliorates
the Th1/Th17 immune response and tissue
injury in chronic rejection. J Heart Lung
Transplant, 36: 175-184.
Zhang Y, Zeng Y. 2019. Curcumin reduces
inflammation in knee osteoarthritis rats
through blocking TLR4/MyD88/NFkappaB signal pathway. Drug Dev Res, 80:
353-359.
Zheng B, Xi Z, Liu R, Yin W, Sui Z, Ren B,
Miller H, Gong Q, Liu C. 2018. The
function of microRNAs in B-cell
development, lymphoma, and their
potential in clinical practice. Front
Immunol, 9: 936.
Zhu W, Zhang X, Jiang Y, Liu X, Huang L,
Wei Q, Huang Y, Wu W, Gu J. 2020.
Alterations in peripheral T cell and B cell
subsets in patients with osteoarthritis. Clin
Rheumatol, 39: 523-532