MAPK inhibitors protect against early‑stage osteoarthritis by activating autophagy

Osteoclast, which mediates overactive bone resorption, is one of the key factors for bone destruction in rheumatoid arthritis (RA). Existing studies have shown that abnormal miR-143-3p expression was observed in both RA patients and arthritis animals, which can participate in osteoclast differentiation, and mitogen-activated protein kinase (MAPK) signaling pathway was closely related to osteoclast differentiation. The primary objective of the current study was to determine the role of miR-143-3p in the progression of osteoclast differentiation and its relationship with MAPK signaling pathways. The results showed that miR-143-3p inhibited osteoclast differentiation and decreased the levels of M-CSF and RANKL during osteoclast differentiation. miR-143-3p inhibited the expression of MAPK signaling proteins, which is ERK1/2 in the early stage and JNK in the later stage of osteoclast differentiation. It was also observed that MAPK inhibitors upregulated miR-143-3p expression in osteoclast differentiation. Taken together, our results suggested that miR-143-3p could inhibit the differentiation of osteoclast, which was related to inhibiting MAPK signaling pathways. This may provide a novel strategy for curing RA.

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Alterations in the number of motoneurons containing immunoreactive calcitonin gene-related peptide(CGRP)& choline acetyltransferase(ChAT) in the cervical spinal cord of the wobbler mouse during the development of the motoneuron disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141226 ◽

1995 ◽

Vol 53 ◽

pp. 970-971

Author(s):

L. Vacca-Galloway ◽

Y.Q. Zhang ◽

P. Bose ◽

S.H. Zhang

Keyword(s):

Spinal Cord ◽

Early Stage ◽

Cervical Spinal Cord ◽

Wild Type Mouse ◽

Reflex Response ◽

Mouse Strains ◽

Behavioral Tests ◽

Wobbler Mouse ◽

Stage 4 ◽

Stage 1

The Wobbler mouse (wr) has been studied as a model for inherited human motoneuron diseases (MNDs). Using behavioral tests for forelimb power, walking, climbing, and the “clasp-like reflex” response, the progress of the MND can be categorized into early (Stage 1, age 21 days) and late (Stage 4, age 3 months) stages. Age-and sex-matched normal phenotype littermates (NFR/wr) were used as controls (Stage 0), as well as mice from two related wild-type mouse strains: NFR/N and a C57BI/6N. Using behavioral tests, we also detected pre-symptomatic Wobblers at postnatal ages 7 and 14 days. The mice were anesthetized and perfusion-fixed for immunocytochemical (ICC) of CGRP and ChAT in the spinal cord (C3 to C5).Using computerized morphomety (Vidas, Zeiss), the numbers of IR-CGRP labelled motoneurons were significantly lower in 14 day old Wobbler specimens compared with the controls (Fig. 1). The same trend was observed at 21 days (Stage 1) and 3 months (Stage 4). The IR-CGRP-containing motoneurons in the Wobbler specimens declined progressively with age.

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Automated high-resolution microscopy: the approaches so far

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100125312 ◽

1987 ◽

Vol 45 ◽

pp. 58-61

Author(s):

W. O. Saxton

Keyword(s):

High Resolution ◽

Early Stage ◽

Automatic Recording ◽

Microprocessor Control ◽

Alternative Systems ◽

Electron Image ◽

Complete Automation ◽

Analysis System ◽

High Resolution Microscopy

Recent commercial microscopes with internal microprocessor control of all major functions have already demonstrated some of the benefits anticipated from such systems, such as continuous magnification, rotation-free diffraction and magnification, automatic recording of mutually registered focal series, and fewer control knobs. Complete automation of the focusing, stigmating and alignment of a high resolution microscope, allowing focal series to be recorded at preselected focus values as well, is still imminent rather than accomplished, however; some kind of image pick-up and analysis system, fed with the electron image via a TV camera, is clearly essential for this, but several alternative systems and algorithms are still being explored. This paper reviews the options critically in turn, and stresses the need to consider alignment and focusing at an early stage, and not merely as an optional extension to a basic proposal.

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Direct observation of Fe-Al-Zn ternary intermetallic compound and its transformation during the early stage of hot-dip galvanizing

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100151416 ◽

1993 ◽

Vol 51 ◽

pp. 1116-1117

Author(s):

C. S. Lin ◽

W. A. Chiou ◽

M. Meshii

Keyword(s):

Intermetallic Compound ◽

Reaction Rate ◽

Diffusion Rate ◽

Early Stage ◽

Zinc Bath ◽

Steel Sheets ◽

Direct Observations ◽

Solid Iron ◽

Iron And Zinc ◽

Ternary Intermetallic Compound

The galvannealed steel sheets have received ever increased attention because of their excellent post-painting corrosion resistance and good weldability. However, its powdering and flaking tendency during press forming processes strongly impairs its performance. In order to optimize the properties of galvanneal coatings, it is critical to control the reaction rate between solid iron and molten zinc.In commercial galvannealing line, aluminum is added to zinc bath to retard the diffusion rate between iron and zinc by the formation of a thin layer of Al intermetallic compound on the surface of steel at initial hot-dip galvanizing. However, the form of this compound and its transformation are still speculated. In this paper, we report the direct observations of this compound and its transformation.The specimens were prepared in a hot-dip simulator in which the steel was galvanized in the zinc bath containing 0.14 wt% of Al at a temperature of 480 °C for 5 seconds and was quenched by liquid nitrogen.

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Anisotropy of interfacial defects in the initial stage of MOVPE GaAs growth On Si

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100176095 ◽

1990 ◽

Vol 48 (4) ◽

pp. 592-593

Author(s):

C. Vannuffel ◽

C. Schiller ◽

J. P. Chevalier

Keyword(s):

Early Stage ◽

Threading Dislocations ◽

Mbe Growth ◽

Detailed Mechanism ◽

Si Substrates ◽

Initial Stage ◽

Interfacial Defects ◽

Interfacial Dislocations ◽

Step Growth ◽

Essential Problem

Recently, interest has focused on the epitaxy of GaAs on Si as a promising material for electronic applications, potentially for integration of optoelectronic devices on silicon wafers. The essential problem concerns the 4% misfit between the two materials, and this must be accommodated by a network of interfacial dislocations with the lowest number of threading dislocations. It is thus important to understand the detailed mechanism of the formation of this network, in order to eventually reduce the dislocation density at the top of the layers.MOVPE growth is carried out on slightly misoriented, (3.5°) from (001) towards , Si substrates. Here we report on the effect of this misorientation on the interfacial defects, at a very early stage of growth. Only the first stage, of the well-known two step growth process, is thus considered. Previously, we showed that full substrate coverage occured for GaAs thicknesses of 5 nm in contrast to MBE growth, where substantially greater thicknesses are required.

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