Show simple item record

dc.contributor.authorKan, Akinorien_US
dc.contributor.authorIkeda, Toshiyukien_US
dc.contributor.authorFukai, Atsushien_US
dc.contributor.authorNakagawa, Takumien_US
dc.contributor.authorNakamura, Kozoen_US
dc.contributor.authorChung, Ung-ilen_US
dc.contributor.authorKawaguchi, Hiroshien_US
dc.contributor.authorTabin, Clifford Jen_US
dc.date.accessioned2014-03-10T16:17:44Z
dc.date.issued2013en_US
dc.identifier.citationKan, Akinori, Toshiyuki Ikeda, Atsushi Fukai, Takumi Nakagawa, Kozo Nakamura, Ung-il Chung, Hiroshi Kawaguchi, and Clifford J Tabin. 2013. “SOX11 contributes to the regulation of GDF5 in joint maintenance.” BMC Developmental Biology 13 (1): 4. doi:10.1186/1471-213X-13-4. http://dx.doi.org/10.1186/1471-213X-13-4.en
dc.identifier.issn1471-213Xen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11877131
dc.description.abstractBackground: Individual skeletal elements of the vertebrate limbs arise through a segmentation process introducing joints in specific locations. However, the molecular pathways controlling joint formation and subsequent joint maintenance are largely unknown. In this study, we focused on SOX11, and its contribution to the regulation of GDF5, a secreted signal necessary for proper joint formation and postnatal joint homeostasis. Results: Sox11 is initially expressed broadly in the murine cartilage condensations at early stages of skeletal development, but its expression is specifically increased in the forming joint interzone as is forms. SOX11 overexpression can directly activate GDF5 expression both in vitro and in micromass cell cultures prepared from chick limb buds. Conserved SOX family binding sites are present in the 5’ UTR region of the GDF5 gene and we show SOX11 can specifically bind to one of them. While misexpression of Sox11 in developing chick limbs through RCAS virus infection does not induce Gdf5 expression in ectopic locations, it does enhance its expression. To explore the roles of Sox11 in joint homeostasis, we analyzed adult knee joints in an osteoarthritis mouse model where the medial meniscus and the medial collateral ligament were removed. We also analyzed knee joints from human subjects who underwent total knee replacement surgery. We find that SOX11 is mainly expressed in the weight-bearing areas of knee joints, and its expression is decreased in degraded cartilage during progression of knee osteoarthritis in both mice and humans. Conclusions: This work implicates SOX11 as a potential regulator of GDF5 expression in joint maintenance and suggests a possible role in the pathogenesis of osteoarthritis.en
dc.language.isoen_USen
dc.publisherBioMed Centralen
dc.relation.isversionofdoi:10.1186/1471-213X-13-4en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760452/pdf/en
dash.licenseLAAen_US
dc.subjecten
dc.subjectJoint maintenanceen
dc.subjectArticular cartilageen
dc.titleSOX11 contributes to the regulation of GDF5 in joint maintenanceen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalBMC Developmental Biologyen
dash.depositing.authorTabin, Clifford Jen_US
dc.date.available2014-03-10T16:17:44Z
dc.identifier.doi10.1186/1471-213X-13-4*
dash.contributor.affiliatedTabin, Clifford


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record