MicroRNA-488 Regulates Zinc Transporter SLC39A8/ZIP8 During Pathogenesis of Osteoarthritis

Overview

Journal J Biomed Sci

Publisher Biomed Central

Specialty Biology

Date 2013 May 22

PMID 23688035

Citations 45

Authors

Jinsoo Song

Dongkyun Kim

Chang Hoon Lee

Myeung Su Lee

Churl-Hong Chun

Eun-Jung Jin

Affiliations

Soon will be listed here.

Abstract

Background: Even though osteoarthritis (OA) is the most common musculoskeletal dysfunction, there are no effective pharmacological treatments to treat OA due to lack of understanding in OA pathology. To better understand the mechanism in OA pathogenesis and investigate its effective target, we analyzed miRNA profiles during OA pathogenesis and verify the role and its functional targets of miR-488.

Results: Human articular chondrocytes were obtained from cartilage of OA patients undergoing knee replacement surgery and biopsy samples of normal cartilage and the expression profile of miRNA was analyzed. From expression profile, most potent miR was selected and its target and functional role in OA pathogenesis were investigated using target validation system and OA animal model system. Among miRNAs tested, miR-488 was significantly decreased in OA chondrocytes Furthermore, we found that exposure of IL-1β was also suppressed whereas exposure of TGF-β3 induced the induction of miR-488 in human articular chondrocytes isolated from biopsy samples of normal cartilages. Target validation study showed that miR-488 targets ZIP8 and suppression of ZIP8 in OA animal model showed the reduced cartilage degradation. Target validation study showed that miR-488 targets ZIP8 and suppression of ZIP8 in OA animal model showed the reduced cartilage degradation.

Conclusions: miR-488 acts as a positive role for chondrocyte differentiation/cartilage development by inhibiting MMP-13 activity through targeting ZIP-8.

Citing Articles

ZIP8 Regulates Inflammation and Macrophage Polarisation in Intervertebral Disc Degeneration via the Wnt/β-Catenin Pathway.

Xu J, Gu H, Zhou K, Wu L, Zhang Y, Bian C J Cell Mol Med. 2025; 29(4):e70431.

PMID: 39993958 PMC: 11850097. DOI: 10.1111/jcmm.70431.

, , and as Significant Hub Genes in End-Stage Osteoarthritis.

Malakootian M, Gholipour A, Oveisee M Iran J Public Health. 2024; 52(12):2651-2662.

PMID: 38435769 PMC: 10903304. DOI: 10.18502/ijph.v52i12.14326.

Matrine From Sophora Flavescens Attenuates on Collagen-Induced Osteoarthritis by Modulating the Activity of miR-29B-3P/PGRN Axis.

Jin Q, Li Z, Xu Q, Liu Q Physiol Res. 2023; 72(4):475-483.

PMID: 37795890 PMC: 10634563. DOI: 10.33549/physiolres.935052.

The role of TGF-beta3 in cartilage development and osteoarthritis.

Du X, Cai L, Xie J, Zhou X Bone Res. 2023; 11(1):2.

PMID: 36588106 PMC: 9806111. DOI: 10.1038/s41413-022-00239-4.

Long Noncoding RNA, MicroRNA, Zn Transporter Zip14 (Slc39a14) and Inflammation in Mice.

Jimenez-Rondan F, Ruggiero C, Cousins R Nutrients. 2022; 14(23).

PMID: 36501144 PMC: 9740689. DOI: 10.3390/nu14235114.

References

Cardinali B, Castellani L, Fasanaro P, Basso A, Alema S, Martelli F . Microrna-221 and microrna-222 modulate differentiation and maturation of skeletal muscle cells. PLoS One. 2009; 4(10):e7607. PMC: 2762614. DOI: 10.1371/journal.pone.0007607. View

Tchetina E . Developmental mechanisms in articular cartilage degradation in osteoarthritis. Arthritis. 2011; 2011:683970. PMC: 3199933. DOI: 10.1155/2011/683970. View

Miyaki S, Sato T, Inoue A, Otsuki S, Ito Y, Yokoyama S . MicroRNA-140 plays dual roles in both cartilage development and homeostasis. Genes Dev. 2010; 24(11):1173-85. PMC: 2878654. DOI: 10.1101/gad.1915510. View

Thorp B, Anderson I, Jakowlew S . Transforming growth factor-beta 1, -beta 2 and -beta 3 in cartilage and bone cells during endochondral ossification in the chick. Development. 1992; 114(4):907-11. DOI: 10.1242/dev.114.4.907. View

Spector T, MacGregor A . Risk factors for osteoarthritis: genetics. Osteoarthritis Cartilage. 2003; 12 Suppl A:S39-44. DOI: 10.1016/j.joca.2003.09.005. View

Chang T, Mendell J . microRNAs in vertebrate physiology and human disease. Annu Rev Genomics Hum Genet. 2007; 8:215-39. DOI: 10.1146/annurev.genom.8.080706.092351. View

Kim V . Small RNAs: classification, biogenesis, and function. Mol Cells. 2005; 19(1):1-15. View

Iliopoulos D, Malizos K, Oikonomou P, Tsezou A . Integrative microRNA and proteomic approaches identify novel osteoarthritis genes and their collaborative metabolic and inflammatory networks. PLoS One. 2008; 3(11):e3740. PMC: 2582945. DOI: 10.1371/journal.pone.0003740. View

Laurent L . MicroRNAs in embryonic stem cells and early embryonic development. J Cell Mol Med. 2009; 12(6A):2181-8. PMC: 4514098. DOI: 10.1111/j.1582-4934.2008.00513.x. View

10.

Ohgawara T, Kubota S, Kawaki H, Kondo S, Eguchi T, Kurio N . Regulation of chondrocytic phenotype by micro RNA 18a: involvement of Ccn2/Ctgf as a major target gene. FEBS Lett. 2009; 583(6):1006-10. DOI: 10.1016/j.febslet.2009.02.025. View

11.

Kobayashi T, Lu J, Cobb B, Rodda S, McMahon A, Schipani E . Dicer-dependent pathways regulate chondrocyte proliferation and differentiation. Proc Natl Acad Sci U S A. 2008; 105(6):1949-54. PMC: 2538863. DOI: 10.1073/pnas.0707900105. View

12.

Liang Z, Zhuang H, Wang G, Li Z, Zhang H, Yu T . MiRNA-140 is a negative feedback regulator of MMP-13 in IL-1β-stimulated human articular chondrocyte C28/I2 cells. Inflamm Res. 2012; 61(5):503-9. DOI: 10.1007/s00011-012-0438-6. View

13.

Li J, Nahra J, Johnson A, Bunker A, OBrien P, Yue W . Quinazolinones and pyrido[3,4-d]pyrimidin-4-ones as orally active and specific matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis. J Med Chem. 2008; 51(4):835-41. DOI: 10.1021/jm701274v. View

14.

Zhong N, Sun J, Min Z, Zhao W, Zhang R, Wang W . MicroRNA-337 is associated with chondrogenesis through regulating TGFBR2 expression. Osteoarthritis Cartilage. 2012; 20(6):593-602. DOI: 10.1016/j.joca.2012.03.002. View

15.

Dudek K, Lafont J, Martinez-Sanchez A, Murphy C . Type II collagen expression is regulated by tissue-specific miR-675 in human articular chondrocytes. J Biol Chem. 2010; 285(32):24381-7. PMC: 2915673. DOI: 10.1074/jbc.M110.111328. View

16.

Goldring M, Otero M . Inflammation in osteoarthritis. Curr Opin Rheumatol. 2011; 23(5):471-8. PMC: 3937875. DOI: 10.1097/BOR.0b013e328349c2b1. View

17.

Sylvester J, El Mabrouk M, Ahmad R, Chaudry A, Zafarullah M . Interleukin-1 induction of aggrecanase gene expression in human articular chondrocytes is mediated by mitogen-activated protein kinases. Cell Physiol Biochem. 2012; 30(3):563-74. DOI: 10.1159/000341438. View

18.

Oteiza P, Mackenzie G . Zinc, oxidant-triggered cell signaling, and human health. Mol Aspects Med. 2005; 26(4-5):245-55. DOI: 10.1016/j.mam.2005.07.012. View

19.

Egloff C, Hugle T, Valderrabano V . Biomechanics and pathomechanisms of osteoarthritis. Swiss Med Wkly. 2012; 142:w13583. DOI: 10.4414/smw.2012.13583. View

20.

Sulsky S, Carlton L, Bochmann F, Ellegast R, Glitsch U, Hartmann B . Epidemiological evidence for work load as a risk factor for osteoarthritis of the hip: a systematic review. PLoS One. 2012; 7(2):e31521. PMC: 3279372. DOI: 10.1371/journal.pone.0031521. View