Differential expression of transient receptor potential vanilloid receptor 4 protein in osteoarthritis and normal cartilages_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

YAO Wangxiang ^1,2 , DAI Hanhao ¹ , DONG Peilong ¹ ,  GUI Jianchao ¹

1. Department of Sports Medicine and Joint Surgery, the Affiliated Nanjing Hospital of Nanjing Medical University, Nanjing Jiangsu, 210000, P.R.China;
2. Department of Orthopaedics, the Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou Zhejiang, 310006, P.R.China;

Corresponding author：

GUI Jianchao, Email: gui1997@126.com

Keywords：

Osteoarthritis; transient receptor potential vanilloid receptor 4; cartilage; extracellular matrix

DOI：

10.7507/1002-1892.201903056

Video：

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Objective To investigate the differential expression of transient receptor potential vanilloid receptor 4 (TRPV4) protein in the osteoarthritis (OA) and normal cartilages, and explore the role of TRPV4 in the prevention and treatment of OA.Methods The cartilage tissues from the patients of knee OA (OA group) and femoral neck fracture (control group) were taken. In OA group, there were 6 males and 9 females; the age ranged from 55 to 78 years (mean, 69 years); the Kellgren-Lawrence (K-L) score was 3.0±0.8. In control group, there were 5 males and 10 females; the age ranged from 57 to 91 years (mean, 71 years). There was no significant difference in gender and age between the two groups (P>0.05). Western blot, real-time fluorescence quantitative PCR, Masson staining, and immunohistochemical staining were used to detect the difference in protein and mRNA expressions of TRPV4 between the OA and normal cartilages. Then the relationship between the K-L score of OA and the rate of TRPV4-positive cells was analyzed.Results The relative expression of TRPV4 protein and mRNA in OA group were 0.454±0.199 and 2.951±1.200, which were higher than those in control group (0.165±0.074, 1.437±0.682). The difference in relative expression of TRPV4 protein was significant (t=2.718, P=0.026). Histology observation showed that the chondrocytes arranged disorderly in OA group, the structure of extracellular matrix was abnormal, and the cartilage defect reached the deep layer. There were more TRPV4-positive cells in the degenerated tissue, and the rate of TRPV4-positive cells was 37.353%±13.496%. The chondrocytes were arranged well in control group, and the rate of TRPV4-positive cells was only 9.642%±3.284%. There was a significant difference between the two groups (t=7.491, P=0.000). The rate of TRPV4-positive cells in OA group was positively correlated with the OA K-L score (r=0.775, P=0.001).Conclusion The TRPV4 expression increased in OA cartilages that may contribute to the development of OA.

Citation： YAO Wangxiang, DAI Hanhao, DONG Peilong, GUI Jianchao. Differential expression of transient receptor potential vanilloid receptor 4 protein in osteoarthritis and normal cartilages. Chinese Journal of Reparative and Reconstructive Surgery, 2020, 34(1): 63-68. doi: 10.7507/1002-1892.201903056 Copy

1.	董佩龙, 唐晓波, 王健, 等. 关节镜下清理术联合 Ilizarov 牵伸术治疗膝关节骨关节炎近期疗效观察. 中国修复重建外科杂志, 2017, 31(7): 794-798.
2.	Guilak F, Leddy HA, Liedtke W. Transient receptor potential vanilloid 4: the sixth sense of the musculoskeletal system? Ann N Y Acad Sci, 2010, 1192: 404-409.
3.	Liu M, Liu X, Wang L, et al. TRPV4 inhibition improved myelination and reduced glia reactivity and inflammation in a cuprizone-induced mouse model of demyelination. Front Cell Neurosci, 2018, 12: 392.
4.	McNulty AL, Leddy HA, Liedtke W, et al. TRPV4 as a therapeutic target for joint diseases. Naunyn Schmiedebergs Arch Pharmacol, 2015, 388(4): 437-450.
5.	Schiphof D, de Klerk BM, Koes BW, et al. Good reliability, questionable validity of 25 different classification criteria of knee osteoarthritis: a systematic appraisal. J Clin Epidemiol, 2008, 61(12): 1205-1215.
6.	Gan Y, Tu B, Li P, et al. Low magnitude of compression enhances biosynthesis of mesenchymal stem cells towards nucleus pulposus cells via the TRPV4-dependent pathway. Stem Cells Int, 2018, 2018: 7061898.
7.	郭保逢, 秦泗河, 黄野. 膝关节骨关节炎的保膝治疗进展. 中国修复重建外科杂志, 2018, 32(10): 1292-1296.
8.	Wuest SL, Caliò M, Wernas T, et al. Influence of mechanical unloading on articular chondrocyte dedifferentiation. Int J Mol Sci, 2018, 19(5): E1289.
9.	Sadowska A, Kameda T, Krupkova O, et al. Osmosensing, osmosignalling and inflammation: how intervertebral disc cells respond to altered osmolarity. Eur Cell Mater, 2018, 36: 231-250.
10.	Phan MN, Leddy HA, Votta BJ, et al. Functional characterization of TRPV4 as an osmotically sensitive ion channel in porcine articular chondrocytes. Arthritis Rheum, 2009, 60(10): 3028-3037.
11.	Walter BA, Purmessur D, Moon A, et al. Reduced tissue osmolarity increases TRPV4 expression and pro-inflammatory cytokines in intervertebral disc cells. Eur Cell Mater, 2016, 32: 123-136.
12.	Wilusz RE, Zauscher S, Guilak F. Micromechanical mapping of early osteoarthritic changes in the pericellular matrix of human articular cartilage. Osteoarthritis Cartilage, 2013, 21(12): 1895-1903.
13.	Wang C, Yan L, Yan B, et al. Agkistrodon ameliorates pain response and prevents cartilage degradation in monosodium iodoacetate-induced osteoarthritic rats by inhibiting chondrocyte hypertrophy and apoptosis. J Ethnopharmacol, 2019, 231: 545-554.
14.	Lee HP, Stowers R, Chaudhuri O. Volume expansion and TRPV4 activation regulate stem cell fate in three-dimensional microenvironments. Nat Commun, 2019, 10(1): 529.
15.	O'Conor CJ, Leddy HA, Benefield HC, et al. TRPV4-mediated mechanotransduction regulates the metabolic response of chondrocytes to dynamic loading. Proc Nat Acad Sci U S A, 2014, 111(4): 1316-1321.
16.	O'Conor CJ, Ramalingam S, Zelenski NA, et al. Cartilage-specific knockout of the mechanosensory ion channel TRPV4 decreases age-related osteoarthritis. Sci Rep, 2016, 6: 29053.
17.	Hdud IM, Mobasheri A, Loughna PT. Effect of osmotic stress on the expression of TRPV4 and BKCa channels and possible interaction with ERK1/2 and p38 in cultured equine chondrocytes. Am J Physiol Cell Physiol, 2014, 306(11): C1050-1057.
18.	Kohn MD, Sassoon AA, Fernando ND. Classifications in brief: Kellgren-Lawrence classification of osteoarthritis. Clin Orthop Relat Res, 2016, 474(8): 1886-1893.
19.	Lewis R, Barrett-Jolley R. Changes in membrane receptors and ion channels as potential biomarkers for osteoarthritis. Front Physiol, 2015, 6: 357.
20.	Haller JM, Swearingen CA, Partridge D, et al. Intraarticular matrix metalloproteinases and aggrecan degradation are elevated after articular fracture. Clin Orthop Relat Res, 2015, 473(10): 3280-3288.

1. 董佩龙, 唐晓波, 王健, 等. 关节镜下清理术联合 Ilizarov 牵伸术治疗膝关节骨关节炎近期疗效观察. 中国修复重建外科杂志, 2017, 31(7): 794-798.
2. Guilak F, Leddy HA, Liedtke W. Transient receptor potential vanilloid 4: the sixth sense of the musculoskeletal system? Ann N Y Acad Sci, 2010, 1192: 404-409.
3. Liu M, Liu X, Wang L, et al. TRPV4 inhibition improved myelination and reduced glia reactivity and inflammation in a cuprizone-induced mouse model of demyelination. Front Cell Neurosci, 2018, 12: 392.
4. McNulty AL, Leddy HA, Liedtke W, et al. TRPV4 as a therapeutic target for joint diseases. Naunyn Schmiedebergs Arch Pharmacol, 2015, 388(4): 437-450.
5. Schiphof D, de Klerk BM, Koes BW, et al. Good reliability, questionable validity of 25 different classification criteria of knee osteoarthritis: a systematic appraisal. J Clin Epidemiol, 2008, 61(12): 1205-1215.
6. Gan Y, Tu B, Li P, et al. Low magnitude of compression enhances biosynthesis of mesenchymal stem cells towards nucleus pulposus cells via the TRPV4-dependent pathway. Stem Cells Int, 2018, 2018: 7061898.
7. 郭保逢, 秦泗河, 黄野. 膝关节骨关节炎的保膝治疗进展. 中国修复重建外科杂志, 2018, 32(10): 1292-1296.
8. Wuest SL, Caliò M, Wernas T, et al. Influence of mechanical unloading on articular chondrocyte dedifferentiation. Int J Mol Sci, 2018, 19(5): E1289.
9. Sadowska A, Kameda T, Krupkova O, et al. Osmosensing, osmosignalling and inflammation: how intervertebral disc cells respond to altered osmolarity. Eur Cell Mater, 2018, 36: 231-250.
10. Phan MN, Leddy HA, Votta BJ, et al. Functional characterization of TRPV4 as an osmotically sensitive ion channel in porcine articular chondrocytes. Arthritis Rheum, 2009, 60(10): 3028-3037.
11. Walter BA, Purmessur D, Moon A, et al. Reduced tissue osmolarity increases TRPV4 expression and pro-inflammatory cytokines in intervertebral disc cells. Eur Cell Mater, 2016, 32: 123-136.
12. Wilusz RE, Zauscher S, Guilak F. Micromechanical mapping of early osteoarthritic changes in the pericellular matrix of human articular cartilage. Osteoarthritis Cartilage, 2013, 21(12): 1895-1903.
13. Wang C, Yan L, Yan B, et al. Agkistrodon ameliorates pain response and prevents cartilage degradation in monosodium iodoacetate-induced osteoarthritic rats by inhibiting chondrocyte hypertrophy and apoptosis. J Ethnopharmacol, 2019, 231: 545-554.
14. Lee HP, Stowers R, Chaudhuri O. Volume expansion and TRPV4 activation regulate stem cell fate in three-dimensional microenvironments. Nat Commun, 2019, 10(1): 529.
15. O'Conor CJ, Leddy HA, Benefield HC, et al. TRPV4-mediated mechanotransduction regulates the metabolic response of chondrocytes to dynamic loading. Proc Nat Acad Sci U S A, 2014, 111(4): 1316-1321.
16. O'Conor CJ, Ramalingam S, Zelenski NA, et al. Cartilage-specific knockout of the mechanosensory ion channel TRPV4 decreases age-related osteoarthritis. Sci Rep, 2016, 6: 29053.
17. Hdud IM, Mobasheri A, Loughna PT. Effect of osmotic stress on the expression of TRPV4 and BKCa channels and possible interaction with ERK1/2 and p38 in cultured equine chondrocytes. Am J Physiol Cell Physiol, 2014, 306(11): C1050-1057.
18. Kohn MD, Sassoon AA, Fernando ND. Classifications in brief: Kellgren-Lawrence classification of osteoarthritis. Clin Orthop Relat Res, 2016, 474(8): 1886-1893.
19. Lewis R, Barrett-Jolley R. Changes in membrane receptors and ion channels as potential biomarkers for osteoarthritis. Front Physiol, 2015, 6: 357.
20. Haller JM, Swearingen CA, Partridge D, et al. Intraarticular matrix metalloproteinases and aggrecan degradation are elevated after articular fracture. Clin Orthop Relat Res, 2015, 473(10): 3280-3288.

Chinese Journal of Reparative and Reconstructive Surgery

Differential expression of transient receptor potential vanilloid receptor 4 protein in osteoarthritis and normal cartilages

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