ArticleAging cell2024
β-Hydroxybutyrate enhances chondrocyte mitophagy and reduces cartilage degeneration in osteoarthritis via the HCAR2/AMPK/PINK1/Parkin pathway.
Article in Aging cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Effects of anti-aging diets and exercise on age-related musculoskeletal diseases via gut microbiota modulation.Annals of medicine · 2026Review
- Mechanical loading primes MSC-derived exosomes to promote cartilage repair.Bioactive materials · 2026Article
- A biomimetic chondrocyte membrane-camouflaged tFNA nanoplatform for reprogramming the cartilage-synovium axis in osteoarthritis.Materials today. Bio · 2026Article
- Endocrine‑metabolic imbalance drives osteoarthritis: From whole‑joint pathobiology to precision therapy (Review).International journal of molecular medicine · 2026Review
- Bioinformatic identification of THY1 as a target in osteoarthritis and its effects on chondrocyte senescence and apoptosis.Functional & integrative genomics · 2026Article
- [Protective effect and mechanism of TSPAN9-mediated mitocytosis in interleukin-1β-induced rat chondrocyte senescence].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026Article
- The value of targeting ketone body metabolism in inflammatory and autoimmune diseases.Journal of translational medicine · 2026Review
- USP34 attenuates cartilage degradation in temporomandibular joint osteoarthritis by ANT1-mediated mitophagy.JBMR plus · 2026Article
- Targeting mitochondrial quality control in osteoarthritis with GrpE-like 1-loaded synovial mesenchymal stromal/stem cell small extracellular vesicles.World journal of stem cells · 2026Article
- Ketone body β-hydroxybutyrate restores neuronal Tau proteostasis via ketolysis-independent mechanism.bioRxiv : the preprint server for biology · 2026Article
- Gut and Joint Microbiome and Dysbiosis: A New Perspective on the Pathogenesis and Treatment of Osteoarthritis.Pathogens (Basel, Switzerland) · 2026Review
- Traditional Chinese medicine-derived monomers delay osteoarthritis progression by regulating mitochondrial homeostasis.Frontiers in cell and developmental biology · 2026Review
- Large-Scale Production of Secretome From Human Dental Pulp Stem Cells for Articular Cartilage Regeneration.Stem cells international · 2026Article
- Regulatory mechanisms and interactions of mitophagy and ketone body metabolism in cardiac metabolism.Frontiers in cardiovascular medicine · 2026Review
- Immunocytes Play a Crucial Role as Mediators in the Protective Effects of D-β-Hydroxybutyrate Dehydrogenase 1 against Type 2 Diabetes Mellitus: A Mendelian Randomization StudyEndocrine, metabolic & immune disorders drug targets · 2026Article
- ACADL and ADH1B signify ketone body metabolic reprogramming in osteoarthritic synovium: insights from bioinformatics and animal model studies.Frontiers in medicine · 2026Article
- Mitochondrial-targeted therapy for osteoarthritis: Challenges and opportunities from basic research to clinical translation.Frontiers in immunology · 2026Review
- ATP-P2X7R-NLRP3 Axis as a Unifying Mechanism of ATP-Induced Cell Death in Degenerative Bone and Cardiovascular Diseases.Journal of inflammation research · 2026Review
- Unlocking the potential of engineered exosomes for knee osteoarthritis therapy.Frontiers in immunology · 2026Review
- E3 ubiquitin ligases in bone homeostasis: from regulatory mechanisms to skeletal diseases and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
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Authors and funding
5 authors.
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Abstract
Osteoarthritis (OA) is widely recognized as the prevailing joint disease associated with aging. The ketogenic diet (KD) has been postulated to impede the advancement of various inflammatory ailments. β-Hydroxybutyrate (βOHB), a prominent constituent of ketone bodies, has recently been proposed to possess crucial signaling capabilities. In this study, we propose to explore the role and mechanism of βOHB in OA. Tissue staining and inflammatory factor assay were employed to evaluate the impacts of KD and βOHB on OA rats. The oxidative stress conditions in chondrocytes were induced using tert-butyl hydroperoxide (TBHP). The mechanisms were determined using the siRNA of hydroxycarboxylic acid receptor 2 (HCAR2), the antagonist of adenosine monophosphate-activated protein kinase (AMPK), and the inhibitor of mitophagy. The administration of KD demonstrated a reduction in pathological damage to cartilage, as well as a decrease in plasma levels of inflammatory factors. Furthermore, it resulted in an increase in the concentration of βOHB in the blood and synovial fluid. In vitro experiments showed that βOHB facilitated mitophagy and adenosine triphosphate production. Besides, βOHB mitigated chondrocyte senescence, inflammatory factors secretion, extracellular matrix degradation, and apoptosis induced by TBHP. Subsequent investigations indicated that the protective effects of βOHB were no longer observed following the knockdown of HCAR2, the antagonist of AMPK, or the inhibitor of mitophagy. Moreover, in vivo studies suggested that βOHB played a protective role by targeting the HCAR2-AMPK-PINK1 axis. In conclusion, βOHB enhanced chondrocyte mitophagy through the HCAR2/AMPK/PINK1/Parkin pathway, offering a potential therapeutic approach for the treatment of OA.
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