Cell-Free Fat Extract Prevents Tail Suspension-Induced Bone Loss by Inhibiting Osteocyte Apoptosis.

Mingming Xu,Mingwu Deng,Jingke Du,Shuangyan Zhang,Junqi Cui,Hanjun Li,Wenjie Zhang,Shuhong Zhang,Zhifeng Yu

doi:10.3389/fbioe.2022.818572

Abstract

Introduction: As the space field has developed and our population ages, people engaged in space travel and those on prolonged bed rest are at increasing risk for bone loss and fractures. Disuse osteoporosis occurs frequently in these instances, for which the currently available anti-osteoporosis agents are far from satisfactory and have undesirable side effects. CEFFE is a cell-free fraction isolated from nanofat that is enriched with a variety of growth factors, and we aim to investigate its potential therapeutic effects on disuse osteoporosis. Methods: A tail suspension–induced osteoporosis model was applied in this study. Three weeks after tail suspension, CEFFE was intraperitoneally injected, and PBS was used as a control. The trabecular and cortical bone microstructures of the tibia in each group were assessed by μCT after 4 weeks of administration. Osteocyte lacunar-canalicularity was observed by HE and silver staining. In vitro, MLO-Y4 cell apoptosis was induced by reactive oxygen species (ROSUP). TUNEL staining and flow cytometry were used to detect apoptosis. CCK-8 was used to detect cell proliferation, and Western blotting was used to detect MAPK signaling pathway changes. Results: CEFFE increased the bone volume (BV/TV) and trabecular number (Tb.N) of the trabecular bone and increased the thickness of the cortical bone. HE and silver staining results showed that CEFFE reduced the number of empty lacunae and improved the lacuna-canalicular structure. CEFFE promoted osteocyte proliferative capacity in a dose-dependent manner. CEFFE protected MLO-Y4 from apoptosis by activating the serine/threonine-selective protein kinase (ERK) signaling pathways. Conclusion: CEFFE attenuated immobilization-induced bone loss by decreasing osteocyte apoptosis. CEFFE increased the survival of osteocytes and inhibited osteocyte apoptosis by activating the ERK signaling pathway in vitro.

Highlights

As the space field has developed and our population ages, people engaged in space travel and those on prolonged bed rest are at increasing risk for bone loss and fractures
Cell-free fat extract (CEFFE) Improved Bone Mass in Osteoporotic Mice Induced by the Tail Suspension Model
The trabecular bone impairment was ameliorated in the tail suspension (TS) + CEFFE group, with increased bone volume (BV/TV) (%), Tb.N (1/mm), and Conn.Dens levels compared with the TS + vehicle group, but Conn.Dens was not different between the TS + CEFFE and TS + vehicle group

Summary

Introduction

As the space field has developed and our population ages, people engaged in space travel and those on prolonged bed rest are at increasing risk for bone loss and fractures. Long-term bed rest caused by trauma or spinal cord injury is a major cause of disuse osteoporosis (Bloomfield, 1997), and with the development of the space industry worldwide in recent years, astronaut’s bone loss caused by a microgravity environment has gradually attracted attention (LeBlanc et al, 2000). In response to bone loss caused by long-term bed rest and weight loss, previous studies have found that bisphosphonates and traditional antiresorptive agents do not work well in disuse osteoporosis (Li et al, 2004). Seeking a better therapeutic strategy for disuse osteoporosis is still a continuously explored process

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