PMID- 34965999 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 2005-3606 (Print) IS - 2005-5447 (Electronic) IS - 2005-3606 (Linking) VI - 15 IP - 2 DP - 2022 May 30 TI - Human Umbilical Cord Mesenchymal Stem Cells Improve the Necrosis and Osteocyte Apoptosis in Glucocorticoid-Induced Osteonecrosis of the Femoral Head Model through Reducing the Macrophage Polarization. PG - 195-202 LID - 10.15283/ijsc21120 [doi] AB - BACKGROUND AND OBJECTIVES: Apoptosis is an outstanding determinant of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been demonstrated to be associated with apoptosis in diseases models. However, the role of hUC-MSCs in GC-induced ONFH via regulating apoptosis still needs further study. METHODS AND RESULTS: In the present study, a GC-induced ONFH model was built in vivo through a consecutive injection with lipopolysaccharide (LPS) and methylprednisolone. The necrosis and apoptosis of the femoral head was evaluated by histological and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) assay. The level of collagen and TRAP positive cells were determined by Masson and TRAP staining, respectively. M1 macrophage polarization was assessed using immunofluorescence assay. The level of proinflammatory cytokines including tumor necrosis factor (TNF)-alpha, Interleukin (IL)-1beta and IL-6 of femoral head was determined by enzyme-linked immunosorbent assay (ELISA) kits. The protein expression of AKT, mTOR, p-AKT and p-mTOR was detected using western blot assay. The results showed that hUC-MSCs treatment prominently promoted the GC-induced the decrease of the collagen level and the increase of TRAP positive cells. Besides, hUC-MSCs treatment decreased necrosis and apoptosis, macrophage polarization, the level of TNF-alpha, IL-1beta and IL-6, the protein expression of p-AKT and p-mTOR, and the radio of p-AKT to AKT and p-mTOR to mTOR of femoral head in vivo. CONCLUSIONS: Therefore, the present study revealed that hUC-MSCs improved the necrosis and osteocyte apoptosis in GC-induced ONFH model through reducing the macrophage polarization, which was associated with the inhibition of AKT/mTOR signaling pathway. FAU - Tian, Gang AU - Tian G AD - Department of Orthopedics, Weihai Central Hospital Affiliated to Qingdao University & Qingdao University, Weihai, China. FAU - Liu, Chuanjie AU - Liu C AD - Xinxiang Medical University, Xinxiang, China. AD - Weihai Key Laboratory of Autoimmunity & Central Laboratory of Weihai Central Hospital, Weihai, China. FAU - Gong, Qi AU - Gong Q AD - Weihai Key Laboratory of Autoimmunity & Central Laboratory of Weihai Central Hospital, Weihai, China. FAU - Yu, Zhiping AU - Yu Z AD - Department of Sports Medicine, Weihai Central Hospital Affiliated to Qingdao University, Weihai, China. FAU - Wang, Haitao AU - Wang H AD - Department of Trauma Surgery, Weihai Central Hospital Affiliated to Qingdao University, Weihai, China. FAU - Zhang, Daoqiang AU - Zhang D AD - Weihai Key Laboratory of Autoimmunity & Central Laboratory of Weihai Central Hospital, Weihai, China. FAU - Cong, Haibo AU - Cong H AD - Department of Orthopedics, Weihai Central Hospital Affiliated to Qingdao University & Weihai Key Laboratory of Autoimmunity, Weihai, China. LA - eng PT - Journal Article PL - Korea (South) TA - Int J Stem Cells JT - International journal of stem cells JID - 101497587 PMC - PMC9148830 OTO - NOTNLM OT - Apoptosis OT - Glucocorticoid OT - Human umbilical cord mesenchymal stem cells OT - Macrophage polarization OT - Osteonecrosis of the femoral head (ONFH) COIS- Potential Conflict of Interest The authors have no conflicting financial interest. EDAT- 2021/12/31 06:00 MHDA- 2021/12/31 06:01 PMCR- 2021/12/31 CRDT- 2021/12/30 05:27 PHST- 2021/06/28 00:00 [received] PHST- 2021/10/01 00:00 [revised] PHST- 2021/10/25 00:00 [accepted] PHST- 2021/12/31 06:00 [pubmed] PHST- 2021/12/31 06:01 [medline] PHST- 2021/12/30 05:27 [entrez] PHST- 2021/12/31 00:00 [pmc-release] AID - ijsc21120 [pii] AID - ijsc-15-2-195 [pii] AID - 10.15283/ijsc21120 [doi] PST - ppublish SO - Int J Stem Cells. 2022 May 30;15(2):195-202. doi: 10.15283/ijsc21120.