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Joint pain is the defining symptom of osteoarthritis (OA) but its origin and mechanisms remain unclear. Here, we investigated an unprecedented role of osteoclast-initiated subchondral bone remodeling in sensory innervation for OA pain. We show that osteoclasts secrete netrin-1 to induce sensory nerve axonal growth in subchondral bone. Reduction of osteoclast formation by knockout of receptor activator of nuclear factor kappa-B ligand (Rank!) in osteocytes inhibited the growth of sensory nerves into subchondral bone, dorsal root ganglion neuron hyperexcitability, and behavioral measures of pain hypersensitivity in OA mice. Moreover, we demonstrated a possible role for netrin-1 secreted by osteoclasts during aberrant subchondral bone remodeling in inducing sensory innervation and OA pain through its receptor DCC (deleted in colorectal cancer). Importantly, knockout of Netrin1 in tartrate-resistant acid phosphatase-positive (TRAP- positive) osteoclasts or knockdown of Dcc reduces OA pain behavior. In particular, inhibition of osteoclast activity by alendronate modifies aberrant subchondral bone remodeling and reduces innervation and pain behavior at the early stage of OA. These results suggest that intervention of the axonal guidance molecules (e.g., netrin-1) derived from aberrant subchondral bone remodeling may have therapeutic potential for OA pain., Introduction Osteoarthritis (OA) is a common musculoskeletal disease in adults, and it is estimated that it will affect 78 million people by 2040 (1), leading to disability and reduced quality [...]

Chronic spinal cord injury (CSCI) is a catastrophic disease of the central nervous system (CNS), resulting in partial or complete loss of neurological function. N6‐methyladenosine (m6A) is the most common form of reversible posttranslational modification at the RNA level. However, the role of m6A modification in CSCI remains unknown. In this study, we established a CSCI model using a water‐absorbable polyurethane polymer, with behavioral assessment, electrophysiological analysis, and histochemical staining for validation. Methylated RNA immunoprecipitation sequencing (meRIP‐seq) and messenger RNA sequencing (mRNA‐seq) were jointly explored to compare the differences between CSCI spinal tissue and normal spinal tissue. Furthermore, real‐time quantitative reverse transcription pcr (qRT–PCR), western blot analysis, and immunofluorescence staining were used to analyze m6A modification‐related proteins. We found that water‐absorbable polyurethane polymer simulated well chronic spinal cord compression. Basso mouse scale scores and electrophysiological analysis showed continuous neurological function decline after chronic compression of the spinal cord. meRIP‐seq identified 642 differentially modified m6A genes, among which 263 genes were downregulated and 379 genes were upregulated. mRNA‐seq showed that 1544 genes were upregulated and 290 genes were downregulated after CSCI. Gene Ontology terms and enriched Kyoto Encyclopedia of Genes and Genomes pathways were also identified. qRT–PCR, western blotting, and immunofluorescence staining showed that Mettl14, Ythdf1, and Ythdf3 were significantly upregulated after CSCI. Our study revealed a comprehensive profile of m6A modifications in CSCI which may act as a valuable key for future research on CSCI. [ABSTRACT FROM AUTHOR]

This article, titled "[Retracted] MicroRNA-336 directly targets Sox-2 in osteosarcoma to inhibit tumorigenesis," was published in Molecular Medicine Reports in 2017. However, it has since been retracted by the editor due to concerns raised by a reader. The reader pointed out that certain data in the article, specifically in figures 3C and D, as well as the tumor images in figure 4A, were similar to data published in other articles by different authors at different research institutes. The editor contacted the authors for an explanation, but did not receive a reply. The editor apologizes for any inconvenience caused. [Extracted from the article]

Lumbar facet joint osteoarthritis (LFJ OA) is regarded as one of the common causes of low back pain (LBP). The pathogenesis and underlying mechanism of this disease are largely unknown, there is still no effective disease‐modifying therapy. This study aims to investigate the efficacy of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) on the pathogenesis and behavioral signs of LBP in the LFJ OA mouse model. The pathogenetic change in cartilage and aberrant nerve invasion in the subchondral bone of LFJ in a mouse model after treatment with BMSC‐exosomes was evaluated. BMSC‐exosomes could relieve pain via abrogation of aberrant CGRP‐positive nerve and abnormal H‐type vessel formation in the subchondral bone of LFJ. Moreover, BMSC‐exosomes attenuated cartilage degeneration and inhibited tartrate‐resistant acid phosphatase expression and RANKL‐RANK‐TRAF6 signaling activation to facilitate subchondral bone remodeling. These results indicated that BMSC‐exosomes could relive behavioral signs of LBP and pathological processes in LFJ OA. BMSC‐exosomes have a prominent protective effect and might be a potential therapeutic option for the treatment of LFJ OA causing LBP. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:670–679, 2020 [ABSTRACT FROM AUTHOR]