Liver injury severity determines skeletal deterioration: a shared pathophysiological axis between MASLD and osteoarthritis

European Association for the Study of the, L., D. European Association for the Study of, and O. European Association for the Study of, EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024;81(3):492–542.

Noureddin M, et al. Predicting NAFLD prevalence in the United States using National Health and Nutrition Examination Survey 2017–2018 transient elastography data and application of machine learning. Hepatol Commun. 2022;6(7):1537–48.

CAS  Google Scholar 

Wang T, et al. Overall and subgroup prevalence of non-alcoholic fatty liver disease and prevalence of advanced fibrosis in the United States: an updated national estimate in National Health and Nutrition Examination Survey (NHANES) 2011–2018. Ann Hepatol. 2024;29(1): 101154.

Google Scholar 

Younossi ZM, et al. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;77(4):1335–47.

Google Scholar 

Wong VW, et al. Changing epidemiology, global trends and implications for outcomes of NAFLD. J Hepatol. 2023;79(3):842–52.

Google Scholar 

Su YH, et al. Nonalcoholic fatty liver disease is associated with decreased bone mineral density in adults: a systematic review and meta-analysis. J Bone Miner Res. 2023;38(8):1092–103.

CAS  Google Scholar 

Cui A, et al. Causal association of NAFLD with osteoporosis, fracture and falling risk: a bidirectional Mendelian randomization study. Front Endocrinol (Lausanne). 2023;14:1215790.

Google Scholar 

Filip R, Radzki RP, Bienko M. Novel insights into the relationship between nonalcoholic fatty liver disease and osteoporosis. Clin Interv Aging. 2018;13:1879–91.

CAS  Google Scholar 

Guarino M, et al. Osteoporosis across chronic liver disease. Osteoporos Int. 2016;27(6):1967–77.

CAS  Google Scholar 

Binvignat M, et al. The role of obesity and adipose tissue dysfunction in osteoarthritis pain. Nat Rev Rheumatol. 2024;20(9):565–84.

Google Scholar 

Lu Y, et al. Association of non-alcoholic fatty liver disease with self-reported osteoarthritis among the US adults. Arthritis Res Ther. 2024;26(1):40.

CAS  Google Scholar 

Cordoba-Chacon J, et al. Growth hormone inhibits hepatic de novo lipogenesis in adult mice. Diabetes. 2015;64(9):3093–103.

CAS  Google Scholar 

Gahete MD, et al. Elevated GH/IGF-I, due to somatotrope-specific loss of both IGF-I and insulin receptors, alters glucose homeostasis and insulin sensitivity in a diet-dependent manner. Endocrinology. 2011;152(12):4825–37.

CAS  Google Scholar 

Luque RM, et al. Metabolic impact of adult-onset, isolated, growth hormone deficiency (AOiGHD) due to destruction of pituitary somatotropes. PLoS ONE. 2011;6(1): e15767.

CAS  Google Scholar 

Cordoba-Chacon J. Loss of hepatocyte-specific PPARgamma expression ameliorates early events of steatohepatitis in mice fed the methionine and choline-deficient diet. PPAR Res. 2020;2020:9735083.

Google Scholar 

Sarmento-Cabral A, et al. GH directly inhibits steatosis and liver injury in a sex-dependent and IGF1-independent manner. J Endocrinol. 2021;248(1):31–44.

CAS  Google Scholar 

Bouxsein ML, et al. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res. 2010;25(7):1468–86.

Google Scholar 

Poudel SB, et al. Development of primary osteoarthritis during aging in genetically diverse UM-HET3 mice. Arthritis Res Ther. 2024;26(1):118.

CAS  Google Scholar 

Glasson SS, et al. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the mouse. Osteoarthritis Cartilage. 2010;18(Suppl 3):S17-23.

Google Scholar 

Kaneko H, et al. Synovial perlecan is required for osteophyte formation in knee osteoarthritis. Matrix Biol. 2013;32(3–4):178–87.

CAS  Google Scholar 

Mapp PI, et al. Angiogenesis in two animal models of osteoarthritis. Osteoarthritis Cartilage. 2008;16(1):61–9.

CAS  Google Scholar 

Stilgenbauer L, et al. Microglial ER stress response via IRE1alpha regulates diet-induced metabolic imbalance and obesity in mice. Mol Metab. 2025;95: 102128.

CAS  Google Scholar 

Debarba LK, et al. Microglia mediate metabolic dysfunction from common air pollutants through NF-kappaB signaling. Diabetes. 2024;73(12):2065–77.

CAS  Google Scholar 

Schneider A, et al. Growth hormone signaling shapes the impact of environmental temperature on transcriptomic profile of different adipose tissue depots in male mice. J Gerontol A Biol Sci Med Sci. 2022;77(5):941–6.

CAS  Google Scholar 

Stilgenbauer L, et al. Growth hormone receptor (GHR) in AgRP neurons regulates thermogenesis in a sex-specific manner. Geroscience. 2023;45(3):1745–59.

CAS  Google Scholar 

Lee SM, et al. Hepatocyte-specific loss of PPARgamma protects mice from NASH and increases the therapeutic effects of rosiglitazone in the liver. Cell Mol Gastroenterol Hepatol. 2021;11(5):1291–311.

Google Scholar 

Charlton M, et al. Fast food diet mouse: novel small animal model of NASH with ballooning, progressive fibrosis, and high physiological fidelity to the human condition. Am J Physiol Gastrointest Liver Physiol. 2011;301(5):G825–34.

CAS  Google Scholar 

Ganz M, Csak T, Szabo G. High fat diet feeding results in gender specific steatohepatitis and inflammasome activation. World J Gastroenterol. 2014;20(26):8525–34.

Google Scholar 

Ishimoto T, et al. High-fat and high-sucrose (western) diet induces steatohepatitis that is dependent on fructokinase. Hepatology. 2013;58(5):1632–43.

CAS  Google Scholar 

Santoro A, McGraw TE, Kahn BB. Insulin action in adipocytes, adipose remodeling, and systemic effects. Cell Metab. 2021;33(4):748–57.

CAS  Google Scholar 

Drescher HK, et al. The influence of different fat sources on steatohepatitis and fibrosis development in the Western diet mouse model of non-alcoholic steatohepatitis (NASH). Front Physiol. 2019;10:770.

Google Scholar 

Lee SM, et al. Hepatocyte PPARgamma contributes to the progression of non-alcoholic steatohepatitis in male and female obese mice. Cell Mol Life Sci. 2023;80(2):39.

CAS  Google Scholar 

Barchetta I, et al. Liver fibrosis is associated with impaired bone mineralization and microstructure in obese individuals with non-alcoholic fatty liver disease. Hepatol Int. 2023;17(2):357–66.

Google Scholar 

Li M, et al. Association between nonalcoholic fatty liver disease (NAFLD) and osteoporotic fracture in middle-aged and elderly Chinese. J Clin Endocrinol Metab. 2012;97(6):2033–8.

CAS  Google Scholar 

Pan B, et al. Relationship between prevalence and risk of osteoporosis or osteoporotic fracture with non-alcoholic fatty liver disease: a systematic review and meta-analysis. Osteoporos Int. 2022;33(11):2275–86.

Google Scholar 

Wester A, Hagstrom H. Risk of fractures and subsequent mortality in non-alcoholic fatty liver disease: a nationwide population-based cohort study. J Intern Med. 2022;292(3):492–500.

CAS  Google Scholar 

Kim MJ, et al. Relationship between the High Fatty Liver Index and risk of fracture. Gut Liver. 2023;17(1):119–29.

CAS  Google Scholar 

Zhao B. TNF and bone remodeling. Curr Osteoporos Rep. 2017;15(3):126–34.

Google Scholar 

de Boer TN, et al. Serum adipokines in osteoarthritis; comparison with controls and relationship with local parameters of synovial inflammation and cartilage damage. Osteoarthritis Cartilage. 2012;20(8):846–53.

Google Scholar 

Koskinen A, et al. Resistin as a factor in osteoarthritis: synovial fluid resistin concentrations correlate positively with interleukin 6 and matrix metalloproteinases MMP-1 and MMP-3. Scand J Rheumatol. 2014;43(3):249–53.

CAS  Google Scholar 

Lee JH, et al. Resistin is elevated following traumatic joint injury and causes matrix degradation and release of inflammatory cytokines from articular cartilage in vitro. Osteoarthritis Cartilage. 2009;17(5):613–20.

CAS  Google Scholar 

Mu Y, et al. NLRC5 attenuates inflammatory response in IL-1beta-stimulated human osteoarthritis chondrocytes through the NF-kappaB signaling pathway. Aging (Albany NY). 2021;13(16):20651–60.

CAS  Google Scholar 

Sun K, et al. IRF1 regulation of ZBP1 links mitochondrial DNA and chondrocyte damage in osteoarthritis. Cell Commun Signal. 2024;22(1):366.

CAS  Google Scholar 

Carlson EL, Karuppagounder V, Pinamont WJ, Yoshioka NK, Ahmad A, Schott EM, Le Bleu HK, Zuscik MJ, Elbarbary RA, Kamal F. Paroxetine-mediated GRK2 inhibition is a disease-modifying treatment for osteoarthritis. Sci Transl Med. 2021;10;13(580):eaau8491. https://doi.org/10.1126/scitranslmed.aau8491.

Mlost J, Kostrzewa M, Malek N, Starowicz K. Molecular understanding of the activation of CB1 and blockade of TRPV1 receptors: implications for novel treatment strategies in osteoarthritis. Int J Mol Sci. 2018;24;19(2):342. https://doi.org/10.3390/ijms19020342.

Mahr S, et al. Cis- and trans-acting gene regulation is associated with osteoarthritis. Am J Hum Genet. 2006;78(5):793–803.

CAS  Google Scholar 

Tang C, et al. Identification of CIRBP and TRPV4 as immune-related diagnostic biomarkers in osteoarthritis. Int J Gen Med. 2021;14:10235–45.

CAS  Google Scholar 

Gavenis K, et al. Expression of ion channels of the TRP family in articular chondrocytes from osteoarthritic patients: changes between native and in vitro propagated chondrocytes. Mol Cell Biochem. 2009;321(1–2):135–43.

CAS  Google Scholar 

Liu G, et al. Inhibition of transient receptor potential canonical 6 attenuates fibroblast-like synoviocytes mediated synovial inflammation and joint destruction in rheumatoid arthritis. Clin Exp Rheumatol. 2021;39(1):115–24.

Google Scholar 

Al-Modawi RN, Brinchmann JE, Karlsen TA. Multi-pathway protective effects of microRNAs on human chondrocytes in an in vitro model of osteoarthritis. Mol Ther Nucleic Acids. 2019;17:776–90.

CAS  Google Scholar 

Okabe N, et al. Suppressor of TCR signaling-2 (STS-2) suppresses arthritis development in mice. Mod Rheumatol. 2018;28(4):626–36.

CAS  Google Scholar 

Tew SR, et al. Post-transcriptional gene regulation following exposure of osteoarthritic human articular chondrocytes to hyperosmotic conditions. Osteoarthritis Cartilage. 2011;19(8):1036–46.

CAS  Google Scholar 

Sapede D, et al. Cartilage regeneration in zebrafish depends on Nrg1/ErbB signaling pathway. Front Cell Dev Biol. 2023;11:1123299.

Google Scholar 

Yamane S, et al. Proinflammatory role of amphiregulin, an epidermal growth factor family member whose expression is augmented in rheumatoid arthritis patients. J Inflamm (Lond). 2008;5:5.

Google Scholar 

Caliogna L, et al. Pathogenesis of osteoarthritis, rheumatoid arthritis, and hemophilic arthropathy: the role of angiogenesis. Haemophilia. 2024;30(6):1256–64.

CAS 

Comments (0)

No login
gif