Mountain Rebecca V, Langlais Audrie L, Hu Dorothy, Baron Roland, Lary Christine W, Motyl Katherine J
Center for Molecular Medicine, MaineHealth Institute for Research, MaineHealth, Scarborough, ME, USA.
Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME, USA.
bioRxiv. 2023 Jan 28:2023.01.27.525939. doi: 10.1101/2023.01.27.525939.
Social isolation is a potent form of psychosocial stress and is a growing public health concern, particularly among older adults. Even prior to the onset of the COVID-19 pandemic, which has significantly increased the prevalence of isolation and loneliness, researchers have been concerned about a rising "epidemic" of loneliness. Isolation is associated with an increased risk for many physical and mental health disorders and increased overall mortality risk. In addition to social isolation, older adults are also at greater risk for osteoporosis and related fractures. While researchers have investigated the negative effects of other forms of psychosocial stress on bone, including depression and PTSD, the effects of social isolation on bone have not been thoroughly investigated. The aim of this study was to test the hypothesis that social isolation would lead to bone loss in male and female C57BL/6J mice. 16-week-old mice were randomized into social isolation (1 mouse/cage) or grouped housing (4 mice/cage) for four weeks (N=16/group). Social isolation significantly decreased trabecular (BV/TV, BMD, Tb. N., Tb. Th.) and cortical bone (Ct.Th., Ct.Ar., Ct.Ar./Tt.Ar., pMOI, Ct.Por.) parameters in male, but not female mice. Isolated male mice had signs of reduced bone remodeling represented by reduced osteoblast numbers, osteoblast-related gene expression and osteoclast-related gene expression. However, isolated females had increased bone resorption-related gene expression, without any change in bone mass. Overall, our data suggest that social isolation has negative effects on bone in males, but not females, although females showed suggestive effects on bone resorption. These results provide critical insight into the effects of isolation on bone and have key clinical implications as we grapple with the long-term health impacts of the rise in social isolation related to the COVID-19 pandemic.
社会隔离是一种强大的心理社会压力形式，并且日益引起公众对健康的关注，尤其是在老年人中。甚至在新冠疫情爆发之前（疫情显著增加了隔离和孤独的发生率），研究人员就一直担心孤独感呈上升趋势的“流行”现象。隔离与许多身心健康障碍的风险增加以及总体死亡率上升有关。除了社会隔离外，老年人患骨质疏松症和相关骨折的风险也更高。虽然研究人员已经研究了其他形式的心理社会压力对骨骼的负面影响，包括抑郁症和创伤后应激障碍，但社会隔离对骨骼的影响尚未得到充分研究。本研究的目的是检验社会隔离会导致雄性和雌性C57BL/6J小鼠骨质流失这一假设。将16周龄的小鼠随机分为社会隔离组（每笼1只小鼠）或群居组（每笼4只小鼠），为期四周（每组N = 16）。社会隔离显著降低了雄性小鼠的小梁骨（骨体积分数、骨密度、骨小梁数量、骨小梁厚度）和皮质骨（皮质厚度、皮质面积、皮质面积/总面积、极惯性矩、皮质孔隙率）参数，但对雌性小鼠没有影响。隔离的雄性小鼠表现出骨重塑减少的迹象，表现为成骨细胞数量减少、成骨细胞相关基因表达和破骨细胞相关基因表达降低。然而，隔离的雌性小鼠骨吸收相关基因表达增加，骨量没有任何变化。总体而言，我们的数据表明，社会隔离对雄性小鼠的骨骼有负面影响，但对雌性小鼠没有影响，尽管雌性小鼠在骨吸收方面表现出暗示性影响。这些结果为隔离对骨骼的影响提供了关键见解，并在我们应对与新冠疫情相关的社会隔离增加所带来的长期健康影响方面具有重要的临床意义。
