LOXL2 promotes aggrecan and gender-specific anabolic differences to TMJ cartilage.

Scientific Reports
Mustafa TashkandiManish V Bais

Abstract

In the United States, 5-12% of adults have at least one symptom of temporomandibular joint (TMJ) disorders, including TMJ osteoarthritis (TMJ-OA). However, there is no chondroprotective agent that is approved for clinical application. We showed that LOXL2 is elevated in the regenerative response during fracture healing in mice and has a critical role in chondrogenic differentiation. Indeed, LOXL2 is an anabolic effector that attenuates pro-inflammatory signaling in OA cartilage of the TMJ and knee joint, induces chondroprotective and regenerative responses, and attenuates NF-kB signaling. The specific goal of the study was to evaluate if adenoviral delivery of LOXL2 is anabolic to human and mouse TMJ condylar cartilage in vivo and evaluate the protective and anabolic effect on cartilage-specific factors. We employed two different models to assess TMJ-OA. In one model, clinical TMJ-OA cartilage from 5 different samples in TMJ-OA cartilage plugs were implanted subcutaneously in nude mice. Adenovirus LOXL2 -treated implants showed higher mRNA levels of LOXL2, ACAN, and other anabolic genes compared to the adenovirus-Empty-treated implants. Further characterization by RNA-seq analysis showed LOXL2 promotes proteoglycan networks and...Continue Reading

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Citations

Jan 13, 2021·International Journal of Molecular Sciences·Chenshuang Li, Zhong Zheng

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Methods Mentioned

BETA
biopsy
fluorescence microscopy
RNA-seq

Software Mentioned

SAMtools
RNA Express Workflow
STAR
DESeq2
iGenomes
GSEA
Image J
prcomp
Zeiss LSM viewer
Gene Set Enrichment Analysis ( GSEA )

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