# Critical role of Sirtuin 6 (SIRT6) in osteoarthritis chondrocytes: the interaction among various biological processes

**Authors:** Ning Ding, Zongru He, Qingshan Yang

PMC · DOI: 10.1080/07853890.2026.2638000 · 2026-03-05

## TL;DR

This paper reviews how SIRT6, a protein involved in aging processes, plays a key role in regulating osteoarthritis in chondrocytes, suggesting it could be a potential treatment target.

## Contribution

The paper highlights the novel perspective of SIRT6 as a central regulator in multiple biological processes affecting osteoarthritis progression.

## Key findings

- SIRT6 is involved in cartilage inflammation, chondrocyte senescence, and DNA damage repair in osteoarthritis.
- SIRT6 interacts with various cytokines to regulate OA progression in chondrocytes.
- Further research is needed to clarify the detailed mechanisms of SIRT6 in OA.

## Abstract

OA (osteoarthritis) is a joint disease that causes drastic economic and financial burdens on people worldwide. Cartilage destruction and synovial inflammation contribute to joint disability, pain, weakness and deformity. Therefore, treatment of OA based on molecular regulation is important. SIRT6 (Sirtuin 6) possesses deacetylase activity and is responsible for many ageing-related biological processes.

SIRT6 activity is affected by age, inflammation, and oxidative stress. However, there is a need to elucidate its role in OA. Chondrocytes are one of the most essential components of articular cartilage. Increasing evidence indicates that SIRT6 plays a critical role in regulating chondrocyte functions in OA. This review aimed to reveal the mechanisms by which SIRT6 regulates OA in chondrocytes.

SIRT6 is also involved in cartilage inflammation, chondrocyte senescence, redox balance, and DNA damage repair. Various biological processes regulate OA development and progression. SIRT6 regulation is an elaborate network that cannot be dissociated. Although an increasing number of studies have focused on SIRT6 function, more detailed research papers are lacking. Therefore, the interwoven functions of SIRT6 should be investigated in future studies.

This review describes the multi-faceted protective roles of SIRT6 in OA chondrocytes. SIRT6 participates in many biological processes and acts as a key node interacting with many cytokines to regulate OA progression. With further researches, the mechanisms of it will be more explicit and it might be a potential therapeutic target for OA treatment.

The overview of SIRT6 functions in OA chondrocyte.

## Linked entities

- **Genes:** SIRT6 (sirtuin 6) [NCBI Gene 51548]
- **Diseases:** osteoarthritis (MONDO:0005178)

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, JAK3 (Janus kinase 3) [NCBI Gene 3718] {aka JAK-3, JAK3_HUMAN, JAKL, L-JAK, LJAK}, SIRT7 (sirtuin 7) [NCBI Gene 51547] {aka SIR2L7}, GATA3 (GATA binding protein 3) [NCBI Gene 2625] {aka HDR, HDRS}, PARP1 (poly(ADP-ribose) polymerase 1) [NCBI Gene 142] {aka ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1}, ADRB1 (adrenoceptor beta 1) [NCBI Gene 153] {aka ADRB1R, B1AR, BETA1AR, FNSS2, RHR}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, PKM (pyruvate kinase M1/2) [NCBI Gene 5315] {aka CTHBP, HEL-S-30, OIP3, PK3, PKM2, TCB}, STAT5A (signal transducer and activator of transcription 5A) [NCBI Gene 6776] {aka MGF, STAT5}, MMP13 (matrix metallopeptidase 13) [NCBI Gene 4322] {aka CLG3, MANDP1, MDST, MMP-13}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, IL15 (interleukin 15) [NCBI Gene 3600] {aka IL-15}, PRDX1 (peroxiredoxin 1) [NCBI Gene 5052] {aka MSP23, NKEF-A, NKEFA, PAG, PAGA, PAGB}, PRX (periaxin) [NCBI Gene 57716] {aka CMT4F}, SIRT6 (sirtuin 6) [NCBI Gene 51548] {aka SIR2L6, hSIRT6}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, TXNIP (thioredoxin interacting protein) [NCBI Gene 10628] {aka ARRDC6, EST01027, HHCPA78, THIF, VDUP1}, PCK1 (phosphoenolpyruvate carboxykinase 1) [NCBI Gene 5105] {aka PCKDC, PEPCK-C, PEPCK1, PEPCKC}, SMARCA5 (SNF2 related chromatin remodeling ATPase 5) [NCBI Gene 8467] {aka ISWI, SNF2H, WCRF135, hISWI, hSNF2H}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, SIRT4 (sirtuin 4) [NCBI Gene 23409] {aka SIR2L4}, Igf1 (insulin-like growth factor 1) [NCBI Gene 16000] {aka C730016P09Rik, Igf-1, Igf-I}, SIRT2 (sirtuin 2) [NCBI Gene 22933] {aka SIR2, SIR2L, SIR2L2}, SIRT5 (sirtuin 5) [NCBI Gene 23408] {aka SIR2L5}, KEAP1 (kelch like ECH associated protein 1) [NCBI Gene 9817] {aka INrf2, KLHL19}, KAT2A (lysine acetyltransferase 2A) [NCBI Gene 2648] {aka GCN5, GCN5L2, PCAF-b, hGCN5}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CHEK1 (checkpoint kinase 1) [NCBI Gene 1111] {aka CHK1, OZEMA21}, TXN (thioredoxin) [NCBI Gene 7295] {aka TRDX, TRX, TRX1, TXN1, Trx80}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, ISYNA1 (inositol-3-phosphate synthase 1) [NCBI Gene 51477] {aka INO1, INOS, IPS, IPS 1, IPS-1}, FOXO1 (forkhead box O1) [NCBI Gene 2308] {aka FKH1, FKHR, FOXO1A}, Sirt6 (sirtuin 6) [NCBI Gene 50721] {aka 2810449N18Rik, Sir2l6, mSIRT6}, SRXN1 (sulfiredoxin 1) [NCBI Gene 140809] {aka C20orf139, Npn3, SRX, SRX1}, BECN1 (beclin 1) [NCBI Gene 8678] {aka ATG6, VPS30, beclin1}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, SIRT3 (sirtuin 3) [NCBI Gene 23410] {aka SIR2L3}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, H3P16 (H3 histone pseudogene 16) [NCBI Gene 644914] {aka H3.6, H3F3AP6, p21}
- **Diseases:** pain (MESH:D010146), Inflammation (MESH:D007249), weakness (MESH:D018908), Cartilage destruction (MESH:D002357), OA (MESH:D010003), RA (MESH:D001172), arthritis (MESH:D001168), OP (MESH:D010024), bone loss (MESH:D001847), knee and hip osteoarthritis (MESH:D020370), joint pain (MESH:D018771), joint disability (MESH:D007592), synovitis (MESH:D013585), telomere (MESH:C536801), deformity (MESH:D009140), movement disorders (MESH:D009069)
- **Chemicals:** menadione (MESH:D024483), MDL-800 (MESH:C000712978), HT (MESH:C005975), NE (MESH:D009356), GAG (MESH:D006025), H2O2 (MESH:D006861), Ihh (-), DMNQ (MESH:C063002), ROS (MESH:D017382)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12964466/full.md

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Source: https://tomesphere.com/paper/PMC12964466