Laboratory for Molecular Psychosomatics, Clinic for Psychosomatic Medicine and Psychotherapy, University, 89081 Ulm, Germany.
Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany.
Dis Model Mech. 2017 Dec 19;10(12):1399-1409. doi: 10.1242/dmm.030916.
Although a strong association between psychiatric and somatic disorders is generally accepted, little is known regarding the interrelationship between mental and skeletal health. Although depressive disorders have been shown to be strongly associated with osteoporosis and increased fracture risk, evidence from post-traumatic stress disorder (PTSD) patients is less consistent. Therefore, the present study investigated the influence of chronic psychosocial stress on bone using a well-established murine model for PTSD. C57BL/6N mice (7 weeks old) were subjected to chronic subordinate colony housing (CSC) for 19 days, whereas control mice were singly housed. Anxiety-related behavior was assessed in the open-field/novel-object test, after which the mice were euthanized to assess endocrine and bone parameters. CSC mice exhibited increased anxiety-related behavior in the open-field/novel-object test, increased adrenal and decreased thymus weights, and unaffected plasma morning corticosterone. Microcomputed tomography and histomorphometrical analyses revealed significantly reduced tibia and femur lengths, increased growth-plate thickness and reduced mineral deposition at the growth plate, suggesting disturbed endochondral ossification during long-bone growth. This was associated with reduced Runx2 expression in hypertrophic chondrocytes in the growth plate. Trabecular thicknesses and bone mineral density were significantly increased in CSC compared to singly housed mice. Tyrosine hydroxylase expression was increased in bone marrow cells located at the growth plates of CSC mice, implying that local adrenergic signaling might be involved in the effects of CSC on the skeletal phenotype. In conclusion, chronic psychosocial stress negatively impacts endochondral ossification in the growth plate, affecting both longitudinal and appositional bone growth in adolescent mice.
尽管精神和躯体障碍之间存在很强的关联已被普遍接受，但对于精神和骨骼健康之间的相互关系知之甚少。尽管抑郁障碍与骨质疏松症和骨折风险增加密切相关，但来自创伤后应激障碍（PTSD）患者的证据则不太一致。因此，本研究使用已建立的 PTSD 小鼠模型来研究慢性心理社会应激对骨骼的影响。将 7 周龄的 C57BL/6N 小鼠（7 周龄）进行慢性下属群体饲养（CSC）19 天，而对照小鼠则单独饲养。在开放式/新物体测试中评估焦虑相关行为，然后处死小鼠以评估内分泌和骨骼参数。CSC 小鼠在开放式/新物体测试中表现出焦虑相关行为增加、肾上腺增加和胸腺减少，而血浆清晨皮质酮不受影响。微计算机断层扫描和组织形态计量学分析显示胫骨和股骨长度明显缩短、生长板厚度增加和生长板处矿物质沉积减少，表明长骨生长过程中的软骨内骨化受到干扰。这与生长板中肥大软骨细胞中 Runx2 表达减少有关。与单独饲养的小鼠相比，CSC 小鼠的小梁厚度和骨矿物质密度显著增加。CSC 小鼠生长板处骨髓细胞中的酪氨酸羟化酶表达增加，表明局部肾上腺素能信号可能参与 CSC 对骨骼表型的影响。总之，慢性心理社会应激会对生长板中的软骨内骨化产生负面影响，影响青少年小鼠的纵向和附加骨生长。
