Table 1.

Summary of the effects of lipid metabolism on cartilage.

Author, Year	Study Population	Methods	Main Outcomes
Shufang Wu, 2003 [99]	Sprague Dawley rats	Treat with inhibitor of the cholesterol synthesis	Cholesterol production suppression inhibits chondrocyte proliferation, hypertrophy, and differentiation. Cholesterol controls growth plate chondrogenesis and longitudinal bone formation, potentially through enhancing IHH’s action in the growth plate.
H. Kishimoto, 2010 [104]	Bovine articular chondrocytes	Treat with ox-LDL	ox-LDL stimulates the hypertrophy of OA chondrocytes, in part, through binding to LOX-1. The binding of ox-LDL to LOX-1 promotes intracellular ROS generation and oxidative stress in chondrocytes.
Aspasia Tsezou, 2010 [106]	Human chondrocytes with OA	Treat with LXR agonist	In osteoarthritis patients, the expression of ABCA1 and ApoA1 transcriptional regulators LXRa and LXRb was dramatically reduced. LXR agonists enhance cholesterol efflux in chondrocytes with osteoarthritis.
C. Gentili, 2005 [109]	Chick chondrocytes	Treat with LXR/RXR agonists	Chondrocytes manufacture ApoA1 during development, and ligands that activate LXR or RXR may lead to a significant increase in ApoA1 expression and cholesterol efflux in thicker chondrocytes. Other LXR target genes are implicated in cholesterol transport and homeostasis, including ABCA1 and SREBP1. The expression of chondrocyte SAA is inhibited by ligands that activate LXR or RXR and induce ApoA1.
Dominique de Seny, 2015 [110]	Human chondrocytes with OA	Incubation with ApoA1, rhSAA, HDL, LDL	By boosting TLR4 activation, free ApoA1 particles in OA joints may directly or indirectly contribute to the local inflammatory process. ApoA1’s inflammatory characteristics on chondrocytes and fibroblast-like synoviocytes will be influenced by HDL and LDL concentrations that are tightly regulated.
Wouter de Munter, 2013 [112]	LDL receptor-deficient and wild-type control mice with OA	Cholesterol-rich diet	In OA, elevated LDL cholesterol levels stimulate the development of ectopic bone. The underlying process may include TGF -β activation and, to a lesser degree, BMP activation after ox-LDL absorption by synovial intimal macrophages.
W an-Su Choi, 2019 [113]	Mice with OA	High-cholesterol diet vs. regular diet	In osteoarthritic chondrocytes, increased cholesterol absorption, cholesterol hydroxylase levels, and hydroxysterol metabolite synthesis directly activate ROR, contributing to the pathogenesis of OA. Through LOX1-mediated augmentation of CH25H and CYP7B1 absorption and metabolism, increased cholesterol levels in chondrocytes induce experimental OA in mice. The CH25H-CYP7B1-ROR axis of cholesterol metabolism in chondrocytes is a crucial catabolic regulator in the etiology of osteoarthritis.
Margaret Man-Ger Sun, 2020 [114]	Mice primary chondrocytes	Treat with specific LXRagonist	Upon activation by its specific agonist, the LXR-Srebp1-Scd1 axis functions as a cholesterol sensor, lowering the buildup of free cholesterol in cells to mitigate cholesterol’s cytotoxic effects. LXR is activated by its particular agonist, and LXR’s protective impact on OA may be mediated, in part, by increased cholesterol excretion and suppression of chondrocyte hypertrophy.
Fotini Kostopoulou, 2015 [116]	Human cartilage with OA	Treat with TGF-β1	miR-33a may influence the TGF-1/PI3K/Akt signaling pathway via the regulation of Smad7 expression. MiR-33 inhibition in OA chondrocytes raises the levels of ABCA1 and HDL, resulting in a reduction in MMP-13 expression.
Shirou Tabe, 2017 [122]	ATDC5 cells	Silence LPCA4 expression	Other than Col2, Sox9, and Runx2, knockdown of LPCAT4 decreased the mRNA expression of chondrogenic differentiation-related molecules. The expression of LPCAT4 rises during chondrogenic differentiation, and LPCAT4 is implicated in chondrocyte hypertrophy.
Mi-Kyoung Kim, 2006 [124]	Rat primary chondrocytes	Treat with S1P and PhS1P	Sphingosine kinase-1 is the key to the production of S1P from sphingosine. S1P and PhS1P lead to cellular proliferation of rat primary chondrocytes through a ptx-sensitive G-protein-mediated pathway, plc-mediated [Ca2+] increase and activation of MAPKs.
Hongming Miao, 2015 [79]	Male C57BL/6 mice	HFD	In a way reliant on LDH-a, circulating stearic acid elevates lactate levels in plasma and chondrocytes. Stearic acid increases the production of VEGF and cytokines that cause inflammation through a TLR4 pathway and a new lactate/HIF1 pathway.
Oscar lvarez-Garcia, 2014 [80]	Human chondrocytes and fibroblast-like synoviocytes	Human chondrocytes from normal and OA were treated with Palmitate or oleate in combination with IL-1	Palmitate, but not oleate, stimulates IL-1 in normal chondrocytes, causing caspase activation and cell death, and upregulates IL-6 and COX2 in chondrocytes and fibroblast-like synoviocytes through Toll-like receptor-4 signaling.
Daniel edina-Luna, 2017 [81]	Human chondrocytes	Treatment with FFA blend consisting of palmitic and oleic acids vs. control	A high-fat milieu causes cartilage degradation by raising chondrocyte IL-1, ROS, and RNS, promoting autocrine production of IL-6 and IL-8.
Chia-Lung Wu, 2014 [75]	Mice with OA	HFD, rich in SFAs, n-3 PUFAs, n-6 PUFAs	n-3 PUFA supplementation may reduce the effects of obesity on OA and enhance healing. SFAs and omega-6 PUFAs are both harmful in OA following joint damage. SFAs may cause synovial macrophages to release IL-1 and TNF, both of which are implicated in cartilage degradation.
M. Miyamoto, 2003 [88]	Primary chondrocytes from rat rib cartilage	Treat with PGE2	Simultaneous stimulation of EP2 and EP4 induces chondrocyte differentiation
H. Davis Adkisson, 1991 [85]	Cartilage from multiple species	Argentation high-performance liquid chromatographic(AHPLC) separationof fatty acid	Low levels of n-6 PUFAs and high levels of abnormal n-9 fatty acids found in normal cartilage
Kohei Nishitani, 2010 [89]	Human chondrocytes	Treat with PGE2	PGE2 inhibits IL-1β-induced MMP-1 and MMP-13 synthesis through EP4 activation and suppression of MKK4, JNK MAP kinase, and c-JUN phosphorylation.
Sunderajhan Sekar, 2017 [73]	Rat	High-Carbohydrate Supplements with SFAs vs. cornstarch diet	High-fat diet can induce metabolic syndrome in rats. Palmitic acid and stearic acid combined with IL-1 mediate cartilage damage by increasing MMP-13, ADAMTS-4, and ADAMTS-5 gene expression and increase the severity of OA
Sujeong Park, 2022 [74]	ACOT12 knockout mice	Treatment with specific agonists and inhibitors of PPARα	ACOT12 is involved in maintaining cartilage homeostasis. Increased accumulation of acetyl-CoA due to PPARα deficiency leads to stimulation of cartilage-degrading enzymes and chondrocyte apoptosis through regulation of ACOT12.