Publications by authors named "Tenghui Tao"

6 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

Two reactive behaviors of chondrocytes in an IL-1β-induced inflammatory environment revealed by the single-cell RNA sequencing.

Aging (Albany NY) 2021 04 20;13(8):11646-11664. Epub 2021 Apr 20.

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

Objective: To investigate the heterogeneous responses of expanded chondrocytes, which were cultured in an interleukin (IL)-1β -induced inflammatory environment.

Method: Human articular chondrocytes were expanded, , for 13 days and treated with IL-1β for 0, 24, and 48 h. Cells were collected and subjected to single-cell RNA sequencing. Multiple bioinformatics tools were used to determine the signatures that define chondrocyte physiology.

Results: Two major cell clusters with distinct expression patterns were identified at the initial phase and were with heterogeneous variation that coincides with inflammation progress. They transformed into two terminal cell clusters one of which exhibited OA-phenotype and proinflammatory characteristics through two paths, "response-to-inflammation" and "atypical response-to-inflammation", respectively. The involved cell clusters exhibited intrinsic relationship with cell types within native cartilage from OA patients. Genes controlling cell transformation to OA-phenotype were relating to the tumor necrosis factor (TNF) signaling pathway via NFKB, up-regulated KRAS signaling and the IL2/STAT5 signaling pathway and pathways relating to apoptosis and reactive oxygen species.

Conclusion: The expanded chondrocytes under IL-1β-induced inflammatory progression behave heterogeneously. One of the initial cell clusters could transform into a proinflammatory subpopulation through a termed response-to-inflammation path, which may serve as the core target to alleviate OA progression.
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http://dx.doi.org/10.18632/aging.202857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109072PMC
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

Tantalum nanoparticles reinforced polyetheretherketone shows enhanced bone formation.

Mater Sci Eng C Mater Biol Appl 2019 Aug 27;101:232-242. Epub 2019 Mar 27.

Department of Orthopedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China. Electronic address:

Polyetheretherketone (PEEK) has been used in orthopedic surgery for several decades. Numerous methods were invented to alter the properties of PEEK. By adding nanoparticles, fibers, etc., elastic modulus and strength of PEEK can be changed to meet certain demand. In this study, tantalum (Ta), a promising metal, was introduced to modify the properties of PEEK, in which PEEK was reinforced with different contents of tantalum nanoparticles (from 1 wt% to 9 wt%). Mechanical properties and biological functions (both in vitro and in vivo) were then investigated. The highest elastic modulus and compressive strength were observed in 3%Ta-PEEK. Cell experiments as cell adhesion, collagen secretion, biomineralization and osteogenesis related gene expression showed preferable results in 3%Ta-PEEK and 5%Ta-PEEK. Improved bone integration was shown in 3%Ta-PEEK and 5%Ta-PEEK in vivo. Above all, enhanced mechanical properties and promoted bone formation were proved for 3%Ta-PEEK and 5%Ta-PEEK compared to others groups both in vitro and in vivo, suggesting that the addition of tantalum nanoparticles modified the osseointegration ability of PEEK. This composite of tantalum and PEEK could have a clinical potential for orthopedic implants.
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http://dx.doi.org/10.1016/j.msec.2019.03.091DOI Listing
August 2019