Oestreich Arin K, Harasymowicz Natalia S, Savadipour Alireza, Harissa Zainab, Rashidi Neda, Luhmann Meredith K, Kuziez Mohammed, Moley Kelle H, Guilak Farshid
Department of Orthopaedic Surgery, Washington University in St. Louis, St Louis, Missouri, USA.
Shriners Hospitals for Children, St. Louis, Missouri, USA.
J Orthop Res. 2025 Jan;43(1):117-127. doi: 10.1002/jor.25980. Epub 2024 Sep 29.
Osteoarthritis (OA) is a prevalent aging disorder of synovial joints and recent work suggests that a parental high-fat diet increases OA severity following joint injury in offspring. We hypothesized that a maternal high-fat high-sugar (HFHS) diet would promote spontaneous osteoarthritis-related cartilage and bone changes in 1-year-old offspring. Female C57BL/6 J mice were placed on either a chow control or HFHS diet for 6 weeks before mating to a chow-fed C57BL/6 J male and maintained on their assigned diets throughout pregnancy and lactation. Male and female offspring were weaned onto a chow diet, raised to 1 year of age, and evaluated for cartilage and bone changes indicative of OA. However, offspring did not show early signs of OA as measured by histological Mankin scoring, mechanical testing of the pericellular matrix, histological synovitis scoring, or subchondral bone thickening as measured by microcomputed Tomography. On the other hand, male offspring from HFHS-fed dams had reduced trabecular bone quality in the tibial metaphysis and decreased cortical thickness. Although maternal HFHS diet did not impact trabecular or cortical bone quality in tibias of female offspring, the radii of these animals had decreased cortical thickness, increased medullary area, and impaired breaking strength compared to those of control-fed dams. Finally, we evaluated bone quality and strength in male and female F2 offspring and found that the grandmaternal diet modestly impacted radial bone geometry but not strength. Together these results suggest that maternal HFHS diet impairs F1 offspring skeletal integrity in a sex and bone site-specific manner.
骨关节炎（OA）是一种常见的滑膜关节衰老性疾病，最近的研究表明，亲代高脂饮食会增加子代关节损伤后OA的严重程度。我们假设，母体高脂高糖（HFHS）饮食会促进1岁子代出现与骨关节炎相关的自发性软骨和骨骼变化。雌性C57BL/6 J小鼠在与喂食普通饲料的C57BL/6 J雄性小鼠交配前6周，被置于普通饲料对照组或HFHS饮食组，并在整个怀孕和哺乳期维持其指定饮食。雄性和雌性子代断奶后喂食普通饲料，饲养至1岁，并评估其软骨和骨骼变化，以确定是否存在OA。然而，通过组织学曼金评分、细胞周围基质的力学测试、组织学滑膜炎评分或微计算机断层扫描测量的软骨下骨增厚来衡量，子代并未表现出OA的早期迹象。另一方面，来自喂食HFHS饮食母鼠的雄性子代，其胫骨近端干骺端的小梁骨质量降低，皮质厚度减小。尽管母体HFHS饮食并未影响雌性子代胫骨的小梁骨或皮质骨质量，但与喂食对照饮食母鼠的子代相比，这些子代的桡骨皮质厚度减小、髓腔面积增加且抗折断强度受损。最后，我们评估了F2代雄性和雌性子代的骨质量和强度，发现祖母的饮食适度影响了桡骨的几何形状，但未影响其强度。这些结果共同表明，母体HFHS饮食以性别和骨骼部位特异性的方式损害了F1代子代的骨骼完整性。
