Publications by authors named "Dahu Qi"

10 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

Hesperetin suppresses RANKL-induced osteoclastogenesis and ameliorates lipopolysaccharide-induced bone loss.

J Cell Physiol 2019 07 11;234(7):11009-11022. Epub 2018 Dec 11.

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

Destructive bone diseases caused by osteolysis are increasing in incidence. They are characterized by an excessive imbalance of osteoclast formation and activation. During osteolysis, the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways are triggered by receptor activator of NF-κB ligand (RANKL), inflammatory factors, and oxidative stress. Previous studies have indicated that the common flavanone glycoside compound hesperetin exhibits anti-inflammatory and antioxidant activity by inhibition of NF-κB and MAPK signaling pathways. However, the direct relationship between hesperetin and osteolysis remain unclear. In the present study, we investigated the effects of hesperetin on lipopolysaccharide (LPS)-induced osteoporosis and elucidated the related mechanisms. Hesperetin effectively suppressed RANKL-induced osteoclastogenesis, osteoclastic bone resorption, and F-actin ring formation in a dose-dependent manner. It also significantly suppressed the expression of osteoclast-specific markers including tartrate-resistant acid phosphatase, matrix metalloproteinase-9, cathepsin K, c-Fos, and nuclear factor of activated T-cells cytoplasmic 1. Furthermore, it inhibited osteoclastogenesis by inhibiting activation of NF-κB and MAPK signaling, scavenging reactive oxygen species, and activating the nuclear factor E2 p45-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling pathway. Consistent with in vitro results, hesperetin effectively ameliorated LPS-induced bone loss, reduced osteoclast numbers, and decreased the RANKL/OPG ratio in vivo. As such, our results suggest that hesperetin may be a great candidate for developing a novel drug for destructive bone diseases such as periodontal disease, tumor bone metastasis, rheumatoid arthritis, and osteoporosis.
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http://dx.doi.org/10.1002/jcp.27924DOI Listing
July 2019

Chemical concentration measurement in blood serum and urine samples using liquid-core optical fiber Raman spectroscopy.

Appl Opt 2007 Apr;46(10):1726-34

The Institute of Optics, University of Rochester, New York 14627, USA.

We report measurements of chemical concentrations in clinical blood serum and urine samples using liquid-core optical fiber (LCOF) Raman spectroscopy to increase the collected signal strength. Both Raman and absorption spectra were acquired in the near-infrared region using the LCOF geometry. Spectra of 71 blood serum and 61 urine samples were regressed via partial least squares against reference analyzer values. Significant correlation was found between predicted and reference concentrations for 13 chemicals. Using absorption data to normalize the LCOF enhancement made the results more accurate. The experimental geometry is well suited for high-volume and automated chemical analysis of clear biofluids.
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http://dx.doi.org/10.1364/ao.46.001726DOI Listing
April 2007

Correction method for absorption-dependent signal enhancement by a liquid-core optical fiber.

Appl Opt 2006 Jan;45(3):489-94

University of Rochester, Rochester, New York 14627, USA.

The enhancement of a dissolved chemical's Raman scattering by a liquid-core optical fiber (LCOF) geometry is absorption dependent. This dependence leads to a disruption of the usual linear correlation between chemical concentration and Raman peak area. To recover the linearity, we augmented a standard LCOF Raman spectroscopy system with spectrophotometric capabilities, permitting sequential measurements of Raman and absorption spectra within the LCOF. Measurements of samples with identical Raman-scatterer concentrations but different absorption coefficients are described. Using the absorption values, we reduced variations in the measured Raman intensities from 60% to less than 1%. This correction method should be important for LCOF-based Raman spectroscopy of sample sets with variable absorption coefficients, such as urine and blood serum from multiple patients.
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http://dx.doi.org/10.1364/ao.45.000489DOI Listing
January 2006

Quantitative concentration measurements of creatinine dissolved in water and urine using Raman spectroscopy and a liquid core optical fiber.

J Biomed Opt 2005 May-Jun;10(3):031115

University of Rochester, The Institute of Optics, Department of Physics and Astronomy, Rochester, New York 14627, USA.

We describe the use of a Teflon-AF liquid core optical fiber (LCOF) geometry to enhance the collection of Raman scattering from the biochemical creatinine, dissolved in water and in urine. At short integration times, where shot noise is most troublesome, the enhanced signal leads to greater accuracy in estimating the creatinine concentration from the spectrum. At longer integration times, instabilities in the LCOF geometry manifest themselves, and the predictions are the same as or worse than those from standard cuvette-based spectral measurements. Photobleaching of fluorescence from urine is more extensive and more stable in the LCOF as well. Starting from the measured enhancement of a major creatinine Raman band, we calculate the expected ratio of prediction errors obtained using the two geometries, and it agrees closely with the observed ratio. These results indicate that Raman spectroscopy with these Teflon-AF LCOFs is stable enough for quantitative concentration predictions, accurate to a few percent of the concentration range spanned.
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http://dx.doi.org/10.1117/1.1917842DOI Listing
November 2005

Quantitative analysis of Raman signal enhancement from aqueous samples in liquid core optical fibers.

Appl Spectrosc 2004 Oct;58(10):1165-71

The Institute of Optics, University of Rochester, Rochester, New York 14627, USA.

Raman scattering from aqueous liquids can be collected with high efficiency by enclosing the liquid within a suitable waveguide, as several groups have reported. Here, we present a quantitative model that predicts the relative strength of signals collected from (a) a tubular waveguide and (b) a flat-walled cuvette. Experimental measurements of Raman scattering from aqueous ethanol are made using two geometries, a Teflon-AF waveguide and a standard quartz cuvette. The model correctly predicts the enhancements in several ethanol Raman bands provided by the waveguide geometry. This model should be useful in aligning and characterizing liquid core waveguides, whose manufacture is still undergoing refinements. In particular, the model shows that absorption and scattering losses affect the enhancement factor in different ways.
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http://dx.doi.org/10.1366/0003702042336109DOI Listing
October 2004
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