Other
11 Authors
- Liu Y,
- Zboinski EK,
- Tu Q,
- Lian J,
- Zhu ZX,
- Van Dyke TE,
- Luo E,
- Liu S,
- Qiu W,
- Chen JJ,
- Johansson HE
| First Author | Liu Y | Year | 2023 |
| Journal | RNA Biol | Volume | 20 |
| Issue | 1 | Pages | 836-846 |
| PubMed ID | 37953645 | Mgi Jnum | J:350135 |
| Mgi Id | MGI:7661207 | Doi | 10.1080/15476286.2023.2268489 |
| Citation | Liu Y, et al. (2023) Long non-coding RNA APDC plays important regulatory roles in metabolism of bone and adipose tissues. RNA Biol 20(1):836-846 |
| abstractText | The long noncoding RNA (lncR) ANRIL in the human genome is an established genetic risk factor for atherosclerosis, periodontitis, diabetes, and cancer. However, the regulatory role of lncR-ANRIL in bone and adipose tissue metabolism remains unclear. To elucidate the function of lncRNA ANRIL in a mouse model, we investigated its ortholog, AK148321 (referred to as lncR-APDC), located on chr4 of the mouse genome, which is hypothesized to have similar biological functions to ANRIL. We initially revealed that lncR-APDC in mouse bone marrow cells (BMSCs) and lncR-ANRIL in human osteoblasts (hFOBs) are both increased during early osteogenesis. Subsequently, we examined the osteogenesis, adipogenesis, osteoclastogenesis function with lncR-APDC deletion/overexpression cell models. In vivo, we compared the phenotypic differences in bone and adipose tissue between APDC-KO and wild-type mice. Our findings demonstrated that lncR-APDC deficiency impaired osteogenesis while promoting adipogenesis and osteoclastogenesis. Conversely, the overexpression of lncR-APDC stimulated osteogenesis, but impaired adipogenesis and osteoclastogenesis. Furthermore, KDM6B was downregulated with lncR-APDC deficiency and upregulated with overexpression. Through binding-site analysis, we identified miR-99a as a potential target of lncR-APDC. The results suggest that lncR-APDC exerts its osteogenic function via miR-99a/KDM6B/Hox pathways. Additionally, osteoclasto-osteogenic imbalance was mediated by lncR-APDC through MAPK/p38 and TLR4/MyD88 activation. These findings highlight the pivotal role of lncR-APDC as a key regulator in bone and fat tissue metabolism. It shows potential therapeutic for addressing imbalances in osteogenesis, adipogenesis, and osteoclastogenesis. |
