Primary Cilia: A Cellular Regulator of Articular Cartilage Degeneration

Figure 2

A brief diagram of Hh signaling under pathological stimuli. Histone deacetylase 6 (HDAC6) is a tubulin deacetylase that regulates the length of the primary cilia. Under normal conditions, the expression of HDAC6 maintains the length of the primary cilia. When the Hh ligand is not activated, Ptc inhibits SMO activity, puts it in a closed state, increases PKA activity, promotes phosphorylation of the SuFu and Gli complex, processes into a truncated repressor form of Gli repressor (GliR), and suppresses Hh target genes in the nucleus (a). Upon pathological stimulation, HDAC6 expression is abnormally increased, promoting primary ciliary elongation and activating the Hh signaling pathway. When the Hh ligand binds to the Ptc receptor to release inhibition of SMO, Smo inhibits Gli processing, causing the full-length Gli activator (GliA) to enter the nucleus to activate relevant target genes such as ADAMTS5 and RUNX2, which causes changes in OA.

(a)

(b)