Table 6 Sirtuins and extracellular matrix regulation

Emanuel et al. (2018)

An experimental study

Experimental in vivo and in vitro study

The aim to identify markers for disc degeneration and apply these to investigate early degenerative changes due to overloading and katabolic cell activity

In vivo, FTIR was more sensitive than biochemical and histologic analyses in identifying decreased proteoglycan content and increased collagen content in degenerative discs.FTIR analyses also revealed disturbances in the ECM as evidenced by increased collagen entropy. In isolation, the proteoglycan/collagen ratio was decreased by overloading and collagen entropy was increased

Matrix remodeling is the first detectable step towards intervertebral disc degeneration

Lu et al. (2021)

An experimental study

Experimental in vivo and in vitro study

To investigate the role of FGF21 in the progression of OA

FGF21 administration alleviated apoptosis, senescence, and extracellular matrix (ECM) catabolism of the chondrocytes induced by tert-butyl hydroperoxide (TBHP) by mediating autophagy flux. The FGF21-induced autophagy flux enhancement was mediated by the nuclear translocation of TFEB, which occurs due to the activation of the SIRT1-mTOR signaling pathway

FGF21 protects chondrocytes from apoptosis, senescence, and ECM catabolism via autophagy flux upregulation and also reduces OA development in vivo

Lin et al. (2021b)

An experimental study

Experimental in vivo and in vitro study

To explore the specific role of ECH in the occurrence and development of OA and its underlying mechanism in vivo and in vitro

ECH was shown to inhibit tert-butyl hydroperoxide (TBHP-)-induced OS and subsequently reduced the levels of p-PERK/PERK, GRP78, ATF4, p-eIF2α/eIF2α and CHOP in vitro. Meanwhile, ECH decreased MMP13 and ADAMTS5 levels and promoted Aggrecan and Collagen II levels, indicating ECM degradation inhibition. Furthermore, we found that ECH mediated its cellular effects by upregulating Sirt1

ECH can inhibit ER stress and ECM degradation by upregulating Sirt1 in mouse chondrocytes treated with TBHP

Liu et al. (2022)

An experimental study

Experimental in vivo and in vitro study

To explore whether the IL-4/JAK/STAT signaling pathway mediated macrophage polarization was involved in mechanical stimulation induced T-B healing

IL-4 production, activation of the JAK/STAT signaling pathway in macrophages, the ability of macrophages to polarize toward the M2 subtype, and T-B healing quality were significantly enhanced in the treadmill running group. This effect induced by mechanical stimulation was depleted after blockade of the IL-4/JAK/STAT signaling pathway

Mechanical stimulation could accelerate T-B healing via activating the IL-4/JAK/STAT signaling pathway that modulates macrophages to polarize towards M2 subtype

Zhao et al. (2022)

An experimental study

Experimental in vivo and in vitro study

To investigate the role of melatonin(MT) in OA rats

MT therapy protects articular cartilage in vivo

MT could reduce chondrocyte matrix degradation by up-regulating nuclear factor-kB (NF-κB) signaling pathway-dependent expression of SIRT1 and protecting chondrocyte by activating the TGF-β1/Smad2 pathway

Shang et al. (2022)

An experimental study

Experimental in vitro study

The study aims to investigate the possible role of paeonol in chondrocyte inflammation and cartilage protection in osteoarthritis (OA) as well as its regulation of SIRT1

Paeonol enhanced SIRT1 expression to inactivate the NF-κβ signaling pathway, thereby ameliorating inflammatory cytokine secretion, ECM degradation, and chondrocyte apoptosis

The present study confirm the potential of paeonol as a candidate OA drug

Eo et al. (2016)

An experimental study

Experimental in vitro study

To explore the mechanism of PEP-1-sirtuin (SIRT)2 induced dedifferentiation of articular chondrocytes

PEP-1-SIRT2 increased MMP-1 and -13 expression in a dose- and time-dependent manner, and PEP-1-SIRT2 increased phosphorylation of extracellularly regulated kinase (ERK); however, treatment of PD98059 with a mitogen-activated protein kinase inhibitor inhibited PEP-1-SIRT2-induced MMP-1 and -13 expression and dedifferentiation while restoring type II collagen expression in passaged 2 cells with type II collagen expression

PEP-1-SIRT2 promotes MMP-induced dedifferentiation via ERK signaling in articular chondrocytes

Smith et al. (2022)

An experimental study

Experimental in vitro study

To investigate the role of SIRT1 in chondrocyte development

Activation of SIRT1 resulted in a significant increase in ECM gene expression for collagen type II (COL2A1) and aggregated glycans (ACAN), as well as the chondrogenic transcription factors SOX5 and ARID5B

SIRT1 activation positively impacts on the expression of the main ECM proteins, while altering ECM composition and suppressing GAG content during human cartilage development

Kuai et al. (2022)

An experimental study

Experimental in vitro study

The purpose of the present study was to investigate lipopolysaccharide (LPS)-induced IDD progression in human nucleus pulposus cells (NPCs) and its potential mechanism

Evodiamine effectively alleviated LPS-induced NPCs apoptosis and caspase-3 activation and Evo treatment reversed the upregulation of matrix metalloproteinase-13, as well as the downregulation of collagen type II (collagen II), Sry-type high-mobility-group box 9 and aggrecan and reduced the production of pro-inflammatory factors TNF-α and IL-6 in LPS-stimulated NPCs

Evodiamine upregulated SIRT1 and inhibited LPS-induced NPCs apoptosis, extracellular matrix degradation and inflammation by activating the PI3K/Akt pathway

Ma et al. (2021)

An experimental study

Experimental in vitro study

To provide evidence that deacetylated-FOXO4 stabilizes chondrocyte (CH) extracellular matrix (ECM) related to SOX9 activation

FOXO4 protein transcriptionally activates SOX9 expression by binding to its promoter. Under the IL-1β stimulation, FOXO4 acetyl-lysine rate increased, and the SOX9 protein expression decreased, which was alleviated after the supplement of exogenic Sirt1 protein. Meanwhile, Sirt1 overexpression increased the collagen II and aggrecan and reduced the collagen I, collagen X, MMP-13, and ADAMTS-5 mRNA expression. However, the silencing of FOXO4 abolished the Sirt1 induced SOX9 expression and weakened the ECM production stability

FOXO4 acetylation aggravates during the degeneration of CHs, and the deacetylation of FOXO4 by Sirt1 could activate the SOX9 expression and result in maintaining the ECM stability of cartilage

Qian et al. (2022)

An experimental study

Experimental in vitro study

Tto investigate the role and mechanism of circ_0022383 on OA progression

Circ_0022383 was expressed at low levels in cartilage and IL-1β-induced primary chondrocytes from OA patients. circ_0022383 acted as a sponge for miR-3619-5p, which has been shown to target SIRT1. miR-3619-5p inhibition eliminated IL-1β-induced chondrocyte apoptosis, inflammation and ECM degeneration, which were counteracted by SIRT1 silencing

Circ_0022383 protected chondrocytes from IL-1β-induced apoptosis, inflammation and ECM degeneration by miR-3619-5p/SIRT1 axis, inspiring future therapy development for OA prevention

Wang et al. (2016b)

An experimental study

Experimental in vitro study

Investigating the role of SIRT1 in intervertebral disc inflammation

SIRT1 inhibited the induction of mRNA expression of proteases that degrade TNF-α-induced ECM. sIRT1 mRNA and protein expression was refractory to hypoxia and HIF-1α

SIRT1 is not affected by hypoxia and inflammatory cytokines in rat intervertebral discs

Qi et al. (2020)

An experimental study

Experimental in vitro study

To explored the effects and mechanisms of tyrosol on IDD progression in interleukin (IL)-1β-stimulated human nucleus pulposus cells (HNPCs)

Tyrosol attenuated IL-1β-induced reduction in viability, apoptosis and caspase-3/7 activity in HNPCs. Tyrosol treatment abrogated the increase in TNF-α, IL-6, NO, and PGE2 production in IL-1β-treated HNPCs.Sirt1 was upregulated by tyrosol, and Sirt1 silencing inhibited Akt phosphorylation in HNPCs. Sirt1 knockdown attenuated the effects of tyrosol on IL-1β-induced apoptosis, inflammation and ECM remodeling in HNPC

Upregulation of Sirt1 by tyrosol suppressed apoptosis and inflammation and regulated ECM remodeling in IL-1β-stimulated HNPCs through activation of PI3K/Akt pathway

Shen et al. (2016)

An experimental study

Experimental in vitro study

To investigate the effects of SIRT1 on proinflammatory stress and signal transduction pathways induced by interleukin-1β (IL-1β) in human degenerative nucleus pulposus (NP) cells

Direct regulation of SIRT1 expression did not affect the synthesis of extracellular matrix (ECM).SIRT1 overexpression mediated by the lentiviral vector suppressed IL-1β-induced ECM degradation and cell apoptosis

SIRT1 exerts anti-inflammatory effects on IL-1β-mediated NP cell degeneration through the TLR2/SIRT1/NF-κB pathway

Zhang et al. (2022)

An experimental study

Experimental in vivo and in vitro study

This study we aim to explore the function of Ori in IVDD pathological model

Ori treatment in vitro increased SIRT1/AMPK in NPCs, maintained ECM and ER balance and decreased oxidative stress (OS) response

Ori exerts its effects by upregulating AMPK and SIRT1

Xie et al. (2022b)

An experimental study

Experimental in vitro study

The purpose of the present study was to investigate the effect of hyperoside on tumor necrosis factor (TNF)-α-induced IDD progression in human nucleus pulposus cells (NPCs) and its potential mechanism

Hyperoside upregulated sirtuin-1 (SIRT1) and nuclear factor E2-related factor 2 (Nrf2) protein expression, and inhibition of SIRT1 or Nrf2 signaling reversed the protective effect of hyperoside on TNF-α-induced NPCs

Hyperoside ameliorated TNF-α-induced inflammation, extracellular matrix degradation, and endoplasmic reticulum stress-mediated apoptosis, which may be associated with the regulation of the SIRT1/NF-κB and Nrf2/antioxidant responsive element signaling pathways by hyperoside