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Wedelolactone Enhances Osteoblastogenesis but Inhibits Osteoclastogenesis through Sema3A/NRP1/PlexinA1 Pathway

Overview of attention for article published in Frontiers in Pharmacology, October 2016
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Title
Wedelolactone Enhances Osteoblastogenesis but Inhibits Osteoclastogenesis through Sema3A/NRP1/PlexinA1 Pathway
Published in
Frontiers in Pharmacology, October 2016
DOI 10.3389/fphar.2016.00375
Pubmed ID
Authors

Yan-Qiu Liu, Xiao-Fei Han, Jun-Xia Bo, Hui-Peng Ma

Abstract

Bone remodeling balance is maintained by tight coupling of osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Thus, agents with the capacity to regulate osteoblastogenesis and osteoclastogenesis have been investigated for therapy of bone-related diseases such as osteoporosis. In this study, we found that wedelolactone, a compound isolated from Ecliptae herba, and a 9-day incubation fraction of conditioned media obtained from wedelolactone-treated bone marrow mesenchymal stem cell (BMSC) significantly inhibited tartrate-resistant acid phosphatase (TRAP) activity in RANKL-stimulated osteoclastic RAW264.7 cells. Addition of the semaphorin 3A (Sema3A) antibody to the conditioned media partially blocked the medium's inhibitory effects on the RAW264.7 cells. In BMSC, mRNA expression of Sema3A increased in the presence of different wedelolactone concentrations. Blocking Sema3A activity with its antibody reversed wedelolactone-induced alkaline phosphatase activity in BMSC and concurrently enhanced wedelolactone-reduced TRAP activity in osteoclastic RAW264.7 cells. Moreover, in BMSC, wedelolactone enhanced binding of Sema3A with cell-surface receptors, including neuropilin (NRP)1 and plexinA1. Furthermore, nuclear accumulation of β-catenin, a transcription factor acting downstream of wedelolactone-induced Sema3A signaling, was blocked by the Sema3A antibody. In osteoclastic RAW264.7 cells, conditioned media and wedelolactone promoted the formation of plexin A1-NRP1, but conditioned media also caused the sequestration of the plexin A1-DNAX-activating protein 12 (DAP12) complex and suppressed the phosphorylation of phospholipase C (PLC)γ2. These data suggest that wedelolactone promoted osteoblastogenesis through production of Sema3A, thus inducing the formation of a Sema3A-plexinA1-Nrp1 complex and β-catenin activation. In osteoclastic RAW264.7 cells, wedelolactone inhibited osteoclastogenesis through sequestration of the plexinA1-DAP12 complex, induced the formation of plexinA1-Nrp1 complex, and suppressed PLCγ2 activation.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 19 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 3 16%
Student > Bachelor 2 11%
Professor > Associate Professor 2 11%
Student > Ph. D. Student 2 11%
Other 1 5%
Other 2 11%
Unknown 7 37%
Readers by discipline Count As %
Chemistry 4 21%
Biochemistry, Genetics and Molecular Biology 3 16%
Agricultural and Biological Sciences 1 5%
Pharmacology, Toxicology and Pharmaceutical Science 1 5%
Medicine and Dentistry 1 5%
Other 1 5%
Unknown 8 42%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 October 2016.
All research outputs
#20,346,264
of 22,893,031 outputs
Outputs from Frontiers in Pharmacology
#10,125
of 16,195 outputs
Outputs of similar age
#273,551
of 316,298 outputs
Outputs of similar age from Frontiers in Pharmacology
#93
of 160 outputs
Altmetric has tracked 22,893,031 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,195 research outputs from this source. They receive a mean Attention Score of 4.9. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 316,298 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 160 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.