Increased susceptibility of Trpv4-deficient mice to obesity and obesity-induced osteoarthritis with very high-fat diet
- 1Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, USA
- 2Department of Biomedical Engineering, University of North Carolina–Chapel Hill, Chapel Hill, North Carolina, USA
- 3Program in Free Radical Biology and Aging, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
- 4Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
- Correspondence to Dr Farshid Guilak, Department of Orthopaedic Surgery, Duke University Medical Center, 375 MSRB, Box 3093, Durham, NC 27710, USA;
- Accepted 27 October 2012
- Published Online First 23 November 2012
Objective To test the hypotheses that: (1) the transient receptor potential vanilloid 4 (TRPV4) ion channel is protective in the obesity model of osteoarthritis (OA), resulting in more severe obesity-induced OA in Trpv4 knockout (Trpv4−/−) mice; and (2) loss of TRPV4 alters mesodermal stem cell differentiation.
Methods Male Trpv4−/− and wild-type (Trpv4+/+) mice were fed a control or high-fat diet (10% kcal and 60% kcal from fat, respectively) for 22 weeks, at which time spontaneous cage activity and severity of knee OA were evaluated. In addition, the adipogenic, osteogenic and chondrogenic potential of bone marrow-derived (MSC) and adipose-derived (ASC) stem cells from Trpv4−/− and Trpv4+/+ mice were compared.
Results A high-fat diet significantly increased knee OA scores and reduced spontaneous cage activity in Trpv4−/− mice, while also increasing weight gain and adiposity. MSCs from Trpv4−/− mice had decreased adipogenic and osteogenic differentiation potential versus Trpv4+/+ MSCs. ASCs from Trpv4−/− mice had increased adipogenic and osteogenic and reduced chondrogenic differentiation potential versus Trpv4+/+ ASCs.
Conclusions Pan-Trpv4−/− mice develop more severe OA with high-fat feeding, potentially due to more severe diet-induced obesity. The altered differentiation potential of Trpv4−/− progenitor cells may reflect the importance of this ion channel in the maintenance and turnover of mesodermally-derived tissues.