High-fat diet-induced obesity accelerates the progression of spontaneous osteoarthritis in Senescence-Accelerated Mouse Prone 8 (SAMP8)

Chenyang Ding; Dilimulati Yimiti; Yohei Sanada; Yuki Matsubara; Tomoyuki Nakasa; Kiminori Matsubara; Nobuo Adachi; Shigeru Miyaki

doi:10.1093/mr/road069

High-fat diet-induced obesity accelerates the progression of spontaneous osteoarthritis in Senescence-Accelerated Mouse Prone 8 (SAMP8)

Mod Rheumatol. 2023 Jul 31:road069. doi: 10.1093/mr/road069. Online ahead of print.

Authors

Chenyang Ding¹, Dilimulati Yimiti¹, Yohei Sanada^{1

2}, Yuki Matsubara¹, Tomoyuki Nakasa³, Kiminori Matsubara⁴, Nobuo Adachi¹, Shigeru Miyaki^{1

2}

Affiliations

¹ Department of Orthopaedic Surgery, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
² Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan.
³ Department of Artificial Joints and Biomaterials, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
⁴ Department of Human Life Science Education, Graduate School of Education, Hiroshima University, Higashi-Hiroshima, Japan.

PMID: 37522619
DOI: 10.1093/mr/road069

Abstract

Objectives: Aging and obesity are major risk factors for osteoarthritis (OA), a widespread disease currently lacking efficient treatments. Senescence-accelerated mouse prone 8 (SAMP8) display early-onset aging phenotypes, including OA. This study investigates the impacts of high-fat diet (HFD)-induced obesity on OA development in SAMP8.

Methods: SAMP8 at five weeks were fed either a normal chow diet or an HFD for ten weeks to induce obesity. Parameters related to obesity, liver function, and lipid and glucose metabolism were analyzed. At 14 weeks of age, knee joint pathology, bone mineral density, and muscle strength were assessed. Immunohistochemistry and TUNEL staining were performed to evaluate markers for cartilage degeneration and chondrocyte apoptosis.

Results: At 14 weeks of age, HFD-induced obesity increased liver and adipose tissue inflammation in SAMP8 without further exacerbating diabetes. Histological scoring revealed aggravated cartilage, menisci deterioration, and synovitis, while no further loss of bone mineral density or muscle strength was observed. Increased chondrocyte apoptosis was detected in knee joints following HFD feeding.

Conclusions: Ten weeks of HFD feeding promotes spontaneous OA progression in 14-week-old SAMP8, potentially via liver damage subsequent chondrocyte apoptosis. This aging-obese mouse model may prove valuable for further exploration of spontaneous OA pathophysiology.

Keywords: Apoptosis; High-fat diet; Obesity; Osteoarthritis; SAMP8.