Premium
NF‐κB activation in Osteoarthritis Occurs Independent of Primary Cilia Associated Proteins HSP27 and IKK Activity
Author(s) -
Rose Brandon James,
Kooyman David L.,
Porter James,
Woolstenhulme Jonny,
Hanson Romney,
Woodbury Reagan,
Marchant Drew
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06919
Subject(s) - osteoarthritis , cilium , iκb kinase , hsp27 , nf κb , kinase , transcription factor , iκbα , chemistry , nfkb1 , phosphorylation , microbiology and biotechnology , cartilage , downregulation and upregulation , heat shock protein , medicine , endocrinology , signal transduction , biology , hsp70 , pathology , anatomy , biochemistry , gene , alternative medicine
Abnormal or nonfunctioning primary cilia are known to be deleterious in cartilage homeostasis, promoting both abnormal cartilage modeling and early onset osteoarthritis. Two proteins specifically regulated by the primary cilia are involved in modulating transcriptional factor nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) activity; heat shock protein 27 (HSP27) aids in activating NF‐κB by degrading inhibitor of kappa‐B kinase alpha (IκBα), IκB kinase (IKK) phosphorylates and inactivates IκBα, freeing NF‐κB to translocate to the nucleus and initiate transcription of inflammatory genes. We hypothesized, therefore, that HSP27 and IKK would be upregulated in osteoarthritic tissue, which would allude to inflammatory mismanagement by the primary cilia as a possible mechanism. The destabilization of the medial meniscus technique (DMM) was successful in inducing osteoarthritis, as manifest by increased Mankin scores compared to rats undergoing the sham surgery (P = 0.009) and increased prevalence of cyst‐like lesions (P = 0.01). Surprisingly, we found no statistically significant difference in HSP27 (P = 0.768) or IKK (P = 0.214), though a statistically significant increase in NF‐κB expression was observed (P = 0.0000877). We therefore conclude that ciliary intervention in osteoarthritis occurs independent of this mechanism, and propose that future research regarding the role of primary cilia in osteoarthritis center on indirect activation of inflammatory mechanisms.