Publications by authors named "Chuankun Zhou"

7 Publications

  • Page 1 of 1

Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Promotes Inflammation and Accelerates Osteoarthritis by Activating β-Catenin.

Front Cell Dev Biol 2021 9;9:646386. Epub 2021 Apr 9.

Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Osteoarthritis (OA) is a chronic articular disease characterized by cartilage degradation, subchondral bone remodeling and osteophyte formation. Src homology 2 domain-containing protein tyrosine phosphatase (SHP2) has not been fully investigated in the pathogenesis of OA. In this study, we found that SHP2 expression was significantly increased after interleukin-1β (IL-1β) treatment in primary mouse chondrocytes. Inhibition of SHP2 using siRNA reduced MMP3, MMP13 levels, but increased AGGRECAN, COL2A1, SOX9 expression . On the contrary, overexpression of SHP2 exerted the opposite results and promoted cartilage degradation. Mechanistically, SHP2 activated Wnt/β-catenin signaling possibly through directly binding to β-catenin. SHP2 also induced inflammation through activating Mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways. Our studies showed that SHP2 knockdown effectively delayed cartilage destruction and reduced osteophyte formation in the mouse model of OA induced by destabilization of the medial meniscus (DMM). Altogether, our study identifies that SHP2 is a novel and potential therapeutic target of OA.
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http://dx.doi.org/10.3389/fcell.2021.646386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063055PMC
April 2021

Inhibiting Monoacylglycerol Lipase Suppresses RANKL-Induced Osteoclastogenesis and Alleviates Ovariectomy-Induced Bone Loss.

Front Cell Dev Biol 2021 12;9:640867. Epub 2021 Mar 12.

Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Osteoporosis is a common chronic metabolic bone disease characterized by reduced trabecular bone and increased bone fragility. Monoacylglycerol lipase (MAGL) is a lipolytic enzyme to catalyze the hydrolysis of monoglycerides and specifically degrades the 2-arachidonoyl glycerol (2-AG). Previous studies have identified that 2-AG is the mainly source for arachidonic acid and the most abundant endogenous agonist of cannabinoid receptors. Considering the close relationship between inflammatory mediators/cannabinoid receptors and bone metabolism, we speculated that MAGL may play a role in the osteoclast differentiation. In the present study, we found that MAGL protein expression increased during osteoclast differentiation. MAGL knockdown by adenovirus-mediated shRNA in bone marrow-derived macrophages demonstrated the suppressive effects of MAGL on osteoclast formation and bone resorption. In addition, pharmacological inhibition of MAGL by JZL184 suppressed osteoclast differentiation, bone resorption, and osteoclast-specific gene expression. Activation of the Mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways was inhibited by JZL184 and deletion of MAGL. Our study indicated that JZL184 ameliorated bone loss in an ovariectomized mouse model. Furthermore, overexpressing H1 calponin partially alleviated the inhibition caused by JZL184 or MAGL deletion on osteoclastogenesis. Therefore, we conclude that targeting MAGL may be a novel therapeutic strategy for osteoporosis.
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http://dx.doi.org/10.3389/fcell.2021.640867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994615PMC
March 2021

Pristimerin Suppresses RANKL-Induced Osteoclastogenesis and Ameliorates Ovariectomy-Induced Bone Loss.

Front Pharmacol 2020 15;11:621110. Epub 2021 Jan 15.

Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Osteoporosis is characterized by bone loss and destruction of trabecular architecture, which greatly increases the burden on the healthcare system. Excessive activation of osteoclasts is an important cause of osteoporosis, and suppression of osteoclastogenesis is helpful for the treatment of osteoporosis. Pristimerin, a natural compound, possesses numerous pharmacological effects via inactivating the NF-κB and MAPK pathways, which are closely related to osteoclastogenesis process. However, the relationship between Pristimerin and osteoclastogenesis requires further investigation. In this research, we examined the effect of Pristimerin on osteoclastogenesis and investigated the related mechanisms. Our results showed Pristimerin inhibited RANKL-induced osteoclast differentiation and osteoclastic bone resorption , with decreased expression of osteoclastogenesis-related markers including c-Fos, NFATc1, TRAP, Cathepsin K, and MMP-9 at both mRNA and protein levels. Furthermore, Pristimerin suppressed NF-κB and MAPK signaling pathways, reduced reactive oxygen species (ROS) production and activated the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling during osteoclastogenesis. Our experiments showed that Pristimerin remarkably ameliorated ovariectomy-induced bone loss, reduced serum levels of TNF-α, IL-1β, IL-6, and RANKL, and increased serum level of osteoprotegerin (OPG). Therefore, our research indicated that Pristimerin is a potential chemical for the treatment of osteoporosis.
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http://dx.doi.org/10.3389/fphar.2020.621110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898668PMC
January 2021

NR1D1 modulates synovial inflammation and bone destruction in rheumatoid arthritis.

Cell Death Dis 2020 02 18;11(2):129. Epub 2020 Feb 18.

Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia, pannus formation, and cartilage and bone destruction. Nuclear receptor subfamily 1 group D member 1 (NR1D1) functions as a transcriptional repressor and plays a vital role in inflammatory reactions. However, whether NR1D1 is involved in synovial inflammation and joint destruction during the pathogenesis of RA is unknown. In this study, we found that NR1D1 expression was increased in synovial tissues from patients with RA and decreased in RA Fibroblast-like synoviocytes (FLSs) stimulated with IL-1β in vitro. We showed that NR1D1 activation decreased the expression of proinflammatory cytokines and matrix metalloproteinases (MMPs), while NR1D1 silencing exerted the opposite effect. Furthermore, NR1D1 activation reduced reactive oxygen species (ROS) generation and increased the production of nuclear transcription factor E2-related factor 2 (Nrf2)-associated enzymes. Mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways were blocked by the NR1D1 agonist SR9009 but activated by NR1D1 silencing. NR1D1 activation also inhibited M1 macrophage polarization and suppressed osteoclastogenesis and osteoclast-related genes expression. Treatment with NR1D1 agonist SR9009 in collagen-induced arthritis (CIA) mouse significantly suppressed the hyperplasia of synovial, infiltration of inflammatory cell and destruction of cartilage and bone. Our findings demonstrate an important role for NR1D1 in RA and suggest its therapeutic potential.
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http://dx.doi.org/10.1038/s41419-020-2314-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028921PMC
February 2020

Vinpocetine inhibits RANKL-induced osteoclastogenesis and attenuates ovariectomy-induced bone loss.

Biomed Pharmacother 2020 Mar 15;123:109769. Epub 2019 Dec 15.

Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address:

Osteoporosis is a result of impaired bone formation and/or excessive bone resorption. Osteoclasts are the only cells in the body that have a bone resorption function. Inhibiting osteoclast activity and differentiation is a way to treat osteoporosis. The current pharmacological treatment for osteoporosis has many shortcomings, and more effective treatments are needed. Vinpocetine (Vinp), a derivative of the alkaloid vincamine, has been used to treat cerebrovascular disorders and cognitive impairment for a long time. Vinp inhibits mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB)-dependent inflammatory responses and oxidative damage in which osteoclasts are often involved. However, the effects of Vinp on the regulation of osteoclast activity remain unknown. In this study, we found that Vinp significantly inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast and F-actin formation and decreased osteoclastic bone resorption in vitro. Vinp also suppressed the expression of osteoclast-specific genes, including NFATc1, c-Fos, tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinase-9 (MMP-9), and cathepsin K (CTSK) at both the mRNA and protein levels. Vinp reduced activation of NF-κB, MAPK, and AKT signaling during osteoclastogenesis and prevented the production of reactive oxygen species with increased nuclear factor erythroid 2-related factor 2, heme oxygenase 1, and NAD(P)H:quinone acceptor oxidoreductase 1 expression. Animal experiments consistently demonstrated that Vinp treatment significantly attenuated ovariectomy-induced bone loss with a decrease in the osteoclast number and decreases in serum levels of RANKL, TRAP, interleukin-1β, and tumor necrosis factor-alpha, as well as increased serum levels of osteoprotegerin. Taken together, our findings reveal that Vinp may be a potential pharmacological choice for preventing and treating osteoporosis.
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http://dx.doi.org/10.1016/j.biopha.2019.109769DOI Listing
March 2020

Association of rs4552569 and rs17095830 single-nucleotide polymorphisms with susceptibility to ankylosing spondylitis in east Asian population: a meta-analysis.

J Genet 2018 Sep;97(4):825-833

Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095#, Jiefang Ave, Wuhan 430000, Hubei, People's Republic of China.

Several studies have been conducted in east Asian population to evaluate the association between rs4552569 and rs17095830 single-nucleotide polymorphisms (SNPs) with susceptibility to ankylosing spondylitis (AS), but the outcomes are inconsistent. A summary evaluation of the evidence supporting the associations has not been performed. Therefore,we performed this meta-analysis to access whether the two SNPs are related to ankylosing spondylitis. We systematically searched PubMed, EMBASE, Web of Science and Cochrane Library for papers published up until 3 February 2017, to obtain relevant studies using our research strategy. The allele/genotype frequencies were extracted from each study. We calculated the summary odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the associations between the two SNPs and AS risk. Four papers including five studies were obtained for this meta-analysis. The included studies suggested that there was no significant association between rs4552569 SNP and AS (C vs T, OR = 1.08, 95% CI: 0.96-1.22, = 0.20).With regard to rs17095830 SNP, significant association was observed (G vs A, OR = 1.19, 95% CI: 1.06-1.33, = 0.002). Based on a comprehensive analysis of the currently available evidence, rs4552569 SNP is not significantly associated with the predisposition of AS, while rs17095830 SNP is likely a susceptibility variant for AS in east Asian population. Further studies with different population groups are needed to confirm these potential associations.
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September 2018

[RESEARCH PROGRESS OF ROLE OF ESTROGEN AND ESTROGEN RECEPTOR ON ONSET AND PROGRESSION OF ADOLESCENT IDIOPATHIC SCOLIOSIS].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2015 Nov;29(11):1441-5

Objective: To review the recent progress in research on the role of estrogen and estrogen receptor on the onset and progression of adolescent idiopathic scoliosis (AIS).

Methods: The recently published clinical and experimental literature at home and abroad on abnormality of estrogen and its receptor in AIS was reviewed and summarized.

Results: There are many abnormal changes of estrogen and estrogen receptor in most AIS patients, including higher serum estrogen concentration, unusual cellular response to estrogen, late age at menarche, and gene polymorphisms of estrogen receptor, which are closely associated with AIS predisposition, curve severity, and scoliosis progression.

Conclusion: Estrogen and its receptor participate in the onset and progression of AIS by certain mechanisms, but exact mechanism remains indefinite, which needs further research to better define the role of estrogen and its receptor in AIS.
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November 2015