机构：[1]State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.[2]Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA, USA.[3]Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.[4]Stomatological Hospital, Southern Medical University, Guangzhou, Guangdong, China.[5]Center for Clinical and Translational Research, The Forsyth Institute, Cambridge, MA, USA.[6]Department of Oral Medicine, Infection, and Immunity, Faculty of Medicine, Harvard University, Boston, MA, USA.[7]Research and Development, LGC Biosearch Technologies, Petaluma, CA, USA.[8]Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA, USA.
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.
基金：
This work was supported by the National Institutes of Health (NIH) grants [R01 DE25681, DE30074] to Jake Chen, [DE025020] to Thomas Van Dyke, and National Natural Science Foundation of China (82001016) to Yao Liu
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|3 区生物学
小类|4 区生化与分子生物学
最新[2023]版：
大类|3 区生物学
小类|4 区生化与分子生物学
第一作者：
第一作者机构：[1]State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.[2]Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA, USA.
共同第一作者：
通讯作者：
通讯机构：[2]Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA, USA.[8]Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA, USA.
推荐引用方式(GB/T 7714)：
Liu Yao,Zhu Zoe Xiaofang,Zboinski Elissa K,et al.Long non-coding RNA APDC plays important regulatory roles in metabolism of bone and adipose tissues[J].RNA biology.2023,20(1):836-846.doi:10.1080/15476286.2023.2268489.
APA：
Liu Yao,Zhu Zoe Xiaofang,Zboinski Elissa K,Qiu Wei,Lian Junxiang...&Chen Jake Jinkun.(2023).Long non-coding RNA APDC plays important regulatory roles in metabolism of bone and adipose tissues.RNA biology,20,(1)
MLA：
Liu Yao,et al."Long non-coding RNA APDC plays important regulatory roles in metabolism of bone and adipose tissues".RNA biology 20..1(2023):836-846
