circSKIL promotes the ossification of cervical posterior longitudinal ligament by activating the JNK/STAT3 pathway

Abstract

Ossification of the posterior longitudinal ligament (OPLL) is a hyperostotic spinal condition that involves genetic factors as well as non-genetic factors, and its underlying molecular mechanism is largely unknown. Recently, circular RNAs (circRNAs) have been attracting the attention of researchers since they have important regulatory roles in many diseases, including bone metabolism disorders. The present study aimed to investigate the role of circRNA SKI-like proto-oncogene (circSKIL) in OPLL disease progression. First, primary posterior longitudinal ligament cells from patients with cervical spondylotic myelopathy (CSM) without OPLL (control group) and CSM patients with OPLL (OPLL group) were isolated, and the expression levels of circSKIL in ligament cells was found to be significantly increased in the OPLL group compared with control. This result was also confirmed in OPLL tissues. Next, circSKIL was overexpressed in control ligament cells, and the proliferation, mineralization, and osteogenic differentiation of ligament cells were found to be significantly enhanced; the phosphorylation levels of both JNK and STAT3 were upregulated. By contrast, the knockdown of circSKIL in OPLL ligament cells inhibited proliferation, mineralization, and osteogenic differentiation and inactivated the JNK/STAT3 pathway. Therefore, circSKIL may have a significant role in osteogenic differentiation and could serve as a potential target to prevent OPLL progression.

Inhibitory effect and mechanism of Rosiglitazone on M1 type polarization of central microglia in intracerebral hemorrhage mice based on JNK/STAT3 signaling pathway

“…The activation of JNK/STAT3 signaling promoted the inflammation, which was confirmed to regulate the M1 polarization of BV2 cells (Sun et al., 2021 ; Wan & Sun, 2019 ). In addition, our finding found the upregulation of PPAR‐γ was able to inhibit this signaling, which confirmed Rosiglitazone could inhibit microglia M1 polarization through inactivating JNK/STAT3 pathway.…”

circSKIL promotes osteoblastic differentiation of periodontal ligament cells by sponging miR‐532‐5p to activate Notch signaling

“…circCDR1‐AS, by sponging miR‐7, up‐regulated growth differentiation factor 5, which promoted osteoblastic differentiation of PDLCs via activating both Smad and p38 signaling 20 . Sun et al identified the up‐regulation of circSKIL in posterior longitudinal ligament cells from patients suffering from cervical spondylotic myelopathy with ossification of cervical posterior longitudinal ligament (OPLL) and revealed that the ossification‐promoting impacts of circSKIL was mediated through the activation of JNK/STAT3 pathway 21 . Here, we demonstrated the essential and sufficient effects of circSKIL in stimulating the osteoblastic differentiation of PDLCs.…”

Non-coding RNAs in ossification of the posterior longitudinal ligament

“…CircRNA expression profiles in primary posterior longitudinal ligament cells Sun et al (2021) found that circSKIL expression levels were significantly elevated in primary cervical posterior longitudinal ligament cells from patients with OPLL and promoted osteogenic differentiation through the JNK/STAT3 pathway. In addition, the overexpression of circSIKL can also improve the expression levels of RUNX2, ALP, COL I, OCN and OPN, thus proving the role of circSIKL in the ossification of the posterior longitudinal ligament.…”