Osteoarthritis-Like Changes in Bardet–Biedl Syndrome Mutant Ciliopathy Mice (Bbs1M390R/M390R): Evidence for a Role of Primary Cilia in Cartilage Homeostasis and Regulation of Inflammation

Frontiers in Physiology

Michael A. Goodman¹  Anthony E. Sanchez¹  Bradley K. Dorius¹  Arminda Suli¹  Mercedes A. McGee¹  Da Young Baek¹  Joshua M. Coleman¹  Brandon J. Rose¹  Steven J. Glenn¹  Dennis L. Eggett¹  John M. Daines¹  Channing Williams¹  Isaac D. Sheffield¹  David L. Kooyman¹  Val C. Sheffield² 

[1] Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT, United States;Departments of Pediatrics and Ophthalmology, University of Iowa, Iowa City, IA, United States;

关键词: Bardet–Biedl syndrome;    Bbs;    osteoarthritis;    primary cilia;    inflammation;   

DOI  :  10.3389/fphys.2018.00708

来源: DOAJ

【 摘 要 】

Osteoarthritis (OA) is a debilitating inflammation related disease characterized by joint pain and effusion, loss of mobility, and deformity that may result in functional joint failure and significant impact on quality of life. Once thought of as a simple “wear and tear” disease, it is now widely recognized that OA has a considerable metabolic component and is related to chronic inflammation. Defects associated with primary cilia have been shown to be cause OA-like changes in Bardet–Biedl mice. We examined the role of dysfunctional primary cilia in OA in mice through the regulation of the previously identified degradative and pro-inflammatory molecular pathways common to OA. We observed an increase in the presence of pro-inflammatory markers TGFβ-1 and HTRA1 as well as cartilage destructive protease MMP-13 but a decrease in DDR-2. We observed a morphological difference in cartilage thickness in Bbs1M390R/M390R mice compared to wild type (WT). We did not observe any difference in OARSI or Mankin scores between WT and Bbs1M390R/M390R mice. Primary cilia appear to be involved in the upregulation of biomarkers, including pro-inflammatory markers common to OA.

【 授权许可】

Unknown