SGMS1 facilitates osteogenic differentiation of MSCs and strengthens osteogenesis-angiogenesis coupling by modulating Cer/PP2A/Akt pathway
Kai Yang,
Ying-yi Luan,
Shan Wang,
You-sheng Yan,
Yi-peng Wang,
Jue Wu,
Yong-qing Sun,
Jing Zhang,
Wen-qi Chen,
Yu-lan Xiang,
Ze-lu Li,
Dong-liang Zhang,
Cheng-hong Yin
Affiliations
Kai Yang
Prenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China
Ying-yi Luan
Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China
Shan Wang
Medical Innovation Research Division, Chinese PLA General Hospital, Beijing, China
You-sheng Yan
Prenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China
Yi-peng Wang
Prenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China
Jue Wu
Medical Innovation Research Division, Chinese PLA General Hospital, Beijing, China
Yong-qing Sun
Prenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China
Jing Zhang
Prenatal Diagnosis Center, Shijiazhuang Obstetrics and Gynecology Hospital, Key Laboratory of Maternal and Fetal Medicine of Hebei Province, Shijiazhuang, Hebei, China
Wen-qi Chen
Prenatal Diagnosis Center, Shijiazhuang Obstetrics and Gynecology Hospital, Key Laboratory of Maternal and Fetal Medicine of Hebei Province, Shijiazhuang, Hebei, China
Yu-lan Xiang
Department of Orthodontics, Beijing Stomatological Hospital, Capital Medical University School of Stomatology, Capital Medical University, Beijing, China
Ze-lu Li
Department of Orthodontics, Beijing Stomatological Hospital, Capital Medical University School of Stomatology, Capital Medical University, Beijing, China
Dong-liang Zhang
Department of Orthodontics, Beijing Stomatological Hospital, Capital Medical University School of Stomatology, Capital Medical University, Beijing, China; Corresponding author
Cheng-hong Yin
Prenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China; Corresponding author
Summary: Mesenchymal stem cell (MSC)-mediated coupling of osteogenesis and angiogenesis is a critical phenomenon in bone formation. Herein, we investigated the role and mechanism of SGMS1 in the osteogenic differentiation of MSCs and, in combination with osteogenesis and angiogenesis, to discover new therapeutic targets for skeletal dysplasia and bone defects. SGMS1 addition accelerated MSC osteogenic differentiation, whereas SGMS1 silencing suppressed this process. Moreover, SGMS1 overexpression inhibited ceramide (Cer) and promoted sphingomyelin (SM) levels. SM treatment neutralized the suppressive effect of shSGMS1 on osteogenesis. SGMS1 restrained PP2A activity by regulating Cer/SM metabolism and thus enhanced the levels of phosphorylated Akt, Runx2, and vascular endothelial growth factor (VEGF). Furthermore, SGMS1 transcription was regulated by Runx2. SGMS1 increased MSC-mediated angiogenesis by promoting VEGF expression. SGMS1 addition promoted rat bone regeneration in vivo. In conclusion, SGMS1 induces osteogenic differentiation of MSCs and osteogenic-angiogenic coupling through the regulation of the Cer/PP2A/Akt signaling pathway.
