The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Excessive mechanical loading promotes osteoarthritis through the gremlin-1–NF-κB pathway
Open accessAbstract
Exposure of articular cartilage to excessive mechanical loading is deeply involved in the pathogenesis of osteoarthritis. Here, we identify gremlin-1 as a mechanical loading-inducible factor in chondrocytes, detected at high levels in middle and deep layers of cartilage after cyclic strain or hydrostatic pressure loading. Gremlin-1 activates nuclear factor-κB signalling, leading to subsequent induction of catabolic enzymes. In mice intra-articular administration of gremlin-1 antibody or chondrocyte-specific deletion of Gremlin-1 decelerates osteoarthritis development, while intra-articular administration of recombinant gremlin-1 exacerbates this process. Furthermore, ras-related C3 botulinum toxin substrate 1 activation induced by mechanical loading enhances reactive oxygen species (ROS) production. Amongst ROS-activating transcription factors, RelA/p65 induces Gremlin-1 transcription, which antagonizes induction of anabolic genes such as Sox9,Col2a1, and Acan by bone morphogenetic proteins. Thus, gremlin-1 plays essential roles in cartilage degeneration by excessive mechanical loading.
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Metadata
- Authors
- Chang, S. H., Mori, D., Kobayashi, H., Mori, Y., Nakamoto, H., Okada, K., Taniguchi, Y., Sugita, S., Yano, F., Chung, U.-I., Kim-Kaneyama, J.-R., Yanagita, M., Economides, A., Canalis, E., Chen, D., Tanaka, S., & Saito, T.
- Venue
- Nature Communications
- Published
- 2019-03-29
- Volume
- 10
- Issue
- 1
- Pages
- 1442-1442
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2931313255
- Cited by
- 293
- References
- 57
- FWCI
- 19.66
- Type
- journal article
- Language
- en
- Open access
- gold
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- Chang, S. H., Mori, D., Kobayashi, H., Mori, Y., Nakamoto, H., Okada, K., Taniguchi, Y., Sugita, S., Yano, F., Chung, U.-I., Kim-Kaneyama, J.-R., Yanagita, M., Economides, A., Canalis, E., Chen, D., Tanaka, S., & Saito, T. (2019). Excessive mechanical loading promotes osteoarthritis through the gremlin-1–NF-κB pathway. Nature Communications. https://doi.org/10.1038/s41467-019-09491-5
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