Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (10): 1-8.doi: 10.6040/j.issn.1671-7554.0.2022.0439

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Thyroid stimulating hormone promotes chondrocyte differentiation via anti-inflammatory protein CTRP3

ZHANG Weiwei1,2, HUA Fang3, LIANG Chaoshuai2, CHU Miaomiao2, SUN Jiayi4, FRANK Zaucke5, XIN Wei2,4   

  1. 1. Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China;
    2. Central Laboratory, Shandong Provincial Hospital, Shandong First Medical University, Jinan 250021, Shandong, China;
    3. Department of Blood Transfusion, Linyi Peoples Hospital of Shandong Province, Linyi 276003, Shandong, China;
    4. School of Clinical and Basic Medicine, Shandong First Medical University, Jinan 250021, Shandong, China;
    5. Department of Orthopaedics University Hospital Frankfurt, Goethe University 60388, Frankfurt, Germany
  • Published:2022-09-30

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Abstract: Objective To investigate the role of thyroid stimulating hormone(TSH)in the differentiation of primary mouse chondrocytes(PMCs)and the underlying mechanism. Methods The expressions of chondrocyte differentiation markers, including extracellular matrix collagen type Ⅱ(Col Ⅱ)and collagen type Ⅹ(Col Ⅹ), and matrix metalloproteinase 3(MMP3)and matrix metalloproteinase 13(MMP13)were detected on both mRNA and protein levels with qRT-PCR, Western blotting and immunofluorescent staining. The changes of interleukin-1β(IL-1β), interleukin-6(IL-6)and tumor necrosis factor-α(TNFα)were detected in TSH stimulated group and control group with qRT-PCR and ELISA. The differentially expressed genes of PMCs treated with TSH were screened with high-throughput RNA-Seq. PMCs were transfected with C1q/tumor necrosis factor-related protein 3(CTRP3)overexpression plasmid o explore the mechanism of TSH regulating PMCs differentiation. Results TSH upregulated the expressions of MMP3(P=0.016, P<0.001), MMP13(P<0.001), IL-1β(P=0.007, P=0.002), IL-6(P<0.001)and TNFα(P=0.006, P<0.001). The differentially expressed gene CTRP3 was screened out with RNA-seq. After CTRP3 overexpression, the expression of Col Ⅱ in PMCs was increased(F=76.062, F=77.085, F=190.115, P<0.001), while the expression of Col Ⅹ was decreased(F=33.494, F=38.424, F=43.351). Compared with simple TSH stimulation, after CTRP3 overexpression, the expressions of MMP3 (F=88.607, F=214.145, F=135.60), MMP13(F=116.561, F=138.674, F=86.865), IL-1β, IL-6 and TNFα were significantly decreased(P<0.001). Conclusion CTRP3 has a protective effect on TSH-induced differentiation of PMCs, and it may become a promising anti-inflammatory therapeutic target for joint injury in patients with subclinical hypothyroidism(SCH).

Key words: Osteoarthritis, Thyroid stimulating hormone, Primary mouse chondrocytes differentiation, C1q/tumor necrosis factor-related protein 3, Inflammatory cytokines

CLC Number: 

  • R446
[1] Chen D, Shen J, Zhao W, et al. Osteoarthritis: toward a comprehensive understanding of pathological mechanism[J]. Bone Res, 2017, 5: 16044. doi:10.1038/boneres.2016.44
[2] Hunter DJ, Bierma-Zeinstra S. Osteoarthritis[J]. Lancet, 2019, 393(10182):1745-1759.
[3] Krieger CC, Neumann S, Gershengorn MC. TSH/IGF1 receptor crosstalk: mechanism and clinical implications[J]. Pharmacol Ther, 2020, 209: 107502. doi: 10.1016/j.pharmthera.2020.107502.
[4] Pasqualetti G, Pagano G, Rengo G, et al. Subclinical hypothyroidism and cognitive impairment: systematic review and meta-analysis[J]. J Clin Endocrinol Metab, 2015, 100(11): 4240-4248.
[5] Davies T, Marians R, Latif R. The TSH receptor reveals itself[J]. J Clin Invest, 2002, 110(2): 161-164.
[6] 胡晓, 常小倩, 宋延彬. CTRP3研究新进展[J]. 生理科学进展, 2020, 51(4): 299-304.
[7] Elgadi A, Zemack H, Marcus C, et al. Tissue-specific knockout of TSHr in white adipose tissue increases adipocyte size and decreases TSH-induced lipolysis[J]. Biochem Biophys Res Commun, 2010, 393(3): 526-530.
[8] Xin W, Yu Y, Ma Y, et al. Thyroid-stimulating hormone stimulation downregulates autophagy and promotes apoptosis in chondrocytes[J]. Endocr J, 2017, 64(7): 749-757.
[9] Rim YA, Nam Y, Ju JH. The Role of chondrocyte hypertrophy and senescence in osteoarthritis initiation and progression[J]. Int J Mol Sci, 2020, 21(7): 2358. doi: 10.3390/ijms21072358.
[10] Peterson JM, Seldin MM, Wei Z, et al. CTRP3 attenuates diet-induced hepatic steatosis by regulating triglyceride metabolism[J]. Am J Physiol Gastrointest Liver Physiol, 2013, 305(3): G214-G224.
[11] Murayama MA, Kakuta S, Maruhashi T, et al. CTRP3 plays an important role in the development of collagen-induced arthritis in mice[J]. Biochem Biophys Res Commun, 2014, 443(1): 42-48.
[12] Kim MJ, Park EJ, Lee W, et al. Regulation of the transcriptional activation of CTRP3 in chondrocytes by c-Jun[J]. Mol Cell Biochem, 2012, 368(1-2): 111-117.
[13] Cawston TE, Wilson AJ. Understanding the role of tissue degrading enzymes and their inhibitors in development and disease[J]. Best Pract Res Clin Rheumatol, 2006, 20(5): 983-1002.
[14] Yamamoto K, Wilkinson D, Bou-Gharios G. Targeting dysregulation of metalloproteinase activity in osteoarthritis[J]. Calcif Tissue Int, 2021, 109(3): 277-290.
[15] Suh S, Kim DK. Subclinical hypothyroidism and cardiovascular disease[J]. Endocrinol Metab(Seoul), 2015, 30(3): 246-251.
[16] Endo T, Kobayashi T. Expression of functional TSH receptor in white adipose tissues of hyt/hyt mice induces lipolysis in vivo[J]. Am J Physiol Endocrinol Metab, 2012, 302(12): E1569-E1575.
[17] Martinez-deMena R, Anedda A, Cadenas S, et al. TSH effects on thermogenesis in rat brown adipocytes[J]. Mol Cell Endocrinol, 2015, 404: 151-158. doi:10.1016/j.mce.2015.01.028.
[18] Yang C, Lu M, Chen W, et al. Thyrotropin aggravates atherosclerosis by promoting macrophage inflammation in plaques[J]. J Exp Med, 2019, 216(5): 1182-1198.
[19] Luan S, Bi W, Shi S, et al. Thyrotropin receptor signaling deficiency impairs spatial learning and memory in mice[J]. J Endocrinol, 2020, 246(1): 41-55.
[20] Endo T, Kobayashi T. Excess TSH causes abnormal skeletal development in young mice with hypothyroidism via suppressive effects on the growth plate[J]. Am J Physiol Endocrinol Metab, 2013, 305(5): E660-E666.
[21] Bassett JH, Williams AJ, Murphy E, et al. A lack of thyroid hormones rather than excess thyrotropin causes abnormal skeletal development in hypothyroidism[J]. Mol Endocrinol, 2008, 22(2): 501-512.
[22] Schäffler A, Weigert J, Neumeier M, et al. Regulation and function of collagenous repeat containing sequence of 26-kDa protein gene product “cartonectin”[J]. Obesity(Silver Spring), 2007,15(2): 303-313.
[23] Maeda T, Abe M, Kurisu K, et al. Molecular cloning and characterization of a novel gene, CORS26, encoding a putative secretory protein and its possible involvement in skeletal development[J]. J Biol Chem, 2001, 276(5): 3628-3634.
[24] Huang Y, Wan G, Tao J. C1q/TNF-related protein-3 exerts the chondroprotective effects in IL-1β-treated SW1353 cells by regulating the FGFR1 signaling[J]. Biomed Pharmacother, 2017, 85: 41-46. doi: 10.1016/j.biopha.2016.11.128.
[25] Petersen PS, Wolf RM, Lei X, et al. Immunomodulatory roles of CTRP3 in endotoxemia and metabolic stress[J]. Physiol Rep, 2016, 4(5): e12735. doi:10.14814/phy2.12735.
[26] Zhang J, Xu J, Lin X, et al. CTRP3 ameliorates fructose-induced metabolic associated fatty liver disease via inhibition of xanthine oxidase-associated oxidative stress[J]. Tissue Cell, 2021, 72: 101595. doi:10.1016/j.tice.2021.101595.
[27] Hu TY, Li LM, Pan YZ, et al. CTRP3 inhibits high glucose-induced human glomerular mesangial cell dysfunction[J]. J Cell Biochem, 2019, 120(4): 5729-5736.
[28] Gao J, Qian T, Wang W. CTRP3 activates the AMPK/SIRT1-PGC-1α pathway to protect mitochondrial biogenesis and functions in cerebral ischemic stroke[J]. Neurochem Res, 2020, 45(12): 3045-3058.
[29] Lv C, He Y, Wei M, et al. CTRP3 ameliorates cerulein-induced severe acute pancreatitis in mice via SIRT1/NF-κB/p53 axis[J]. Biosci Rep, 2020, 40(10): BSR20200092. doi: 10.1042/BSR20200092.
[30] Zhang R, Zhong L, Zhou J, et al. Complement-C1q TNF-related protein 3 alleviates mesangial cell activation and inflammatory response stimulated by secretory IgA[J]. Am J Nephrol, 2016, 43(6): 460-468.
[31] Qu H, Deng M, Wang H, et al. Plasma CTRP-3 concentrations in Chinese patients with obesity and type II diabetes negatively correlate with insulin resistance[J]. J Clin Lipidol, 2015, 9(3): 289-294.
[32] Ma ZG, Yuan YP, Xu SC, et al. CTRP3 attenuates cardiac dysfunction, inflammation, oxidative stress and cell death in diabetic cardiomyopathy in rats[J]. Diabetologia, 2017, 60(6): 1126-1137.
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