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运动改善雌性分泌型富含半胱氨酸酸性蛋白(SPARC)基因缺失小鼠的承重骨结构特性,但对雄性无影响。

Exercise improves load bearing bone structural properties in female secreted protein acidic and rich in cysteine (SPARC) null mice but not in males.

机构信息

Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center (CSMC), Los Angeles, California, USA.

Board of Governors Regenerative Medicine Institute, CSMC, Los Angeles, California, USA.

出版信息

J Orthop Res. 2024 Dec;42(12):2725-2734. doi: 10.1002/jor.25950. Epub 2024 Aug 6.

DOI:10.1002/jor.25950
PMID:39105654
Abstract

Secreted protein acidic and rich in cysteine (SPARC) is the most abundant glycoprotein in bone and is thought to play a critical role in bone remodeling and homeostasis. However, the effect of SPARC in relation to gender and exercise on bone quality is not well understood. The purpose of this study was to quantify differences in the structural and biomechanical properties between calvarial and femoral bone from male and female wild-type (WT) and SPARC null (SPARC) mice as well as the ability of exercise to rescue bone health. Male and female WT and transgenic SPARC mice were given either a fixed or rotating running wheel for exercise. Bone structural, biomechanical, and morphological parameters were quantified using micro computed tomography, push out testing for the calvaria, three-point flexural testing for the femurs, histological and immunofluorescent staining. Similar reductions in structural and biomechanical strength were observed in both male and female SPARC calvaria, most of which were not significantly affected by exercise. In femurs, SPARC had a significant effect on structural parameters in both sexes, but was more pronounced in females with some properties being rescued with running. Interestingly, the effect of SPARC on bone mineral density was only detected in female SPARC mice, not males, and was subsequently rescued with exercise. This study emphasizes the differences between sexes in WT and SPARC mice in regard to structural parameters and biomechanical properties. Research into gender differences can help inform and personalize treatment options to more accurately meet patient needs.

摘要

富含半胱氨酸的酸性分泌蛋白(SPARC)是骨骼中最丰富的糖蛋白,被认为在骨骼重塑和平衡中发挥着关键作用。然而,SPARC 与性别和运动对骨质量的影响尚不清楚。本研究的目的是定量分析雄性和雌性野生型(WT)和 SPARC 缺失(SPARC)小鼠颅骨和股骨在结构和生物力学特性方面的差异,以及运动对骨骼健康的恢复能力。雄性和雌性 WT 和转基因 SPARC 小鼠分别给予固定或旋转跑轮进行运动。使用微计算机断层扫描、颅骨推挤试验、股骨三点弯曲试验、组织学和免疫荧光染色来定量分析骨结构、生物力学和形态参数。SPARC 对雄性和雌性颅骨的结构和生物力学强度都有相似的降低作用,其中大部分不受运动的显著影响。在股骨中,SPARC 对两性的结构参数都有显著影响,但在雌性中更为明显,有些特性可以通过跑步来恢复。有趣的是,SPARC 对骨密度的影响仅在雌性 SPARC 小鼠中检测到,而在雄性中未检测到,随后通过运动得到恢复。本研究强调了 WT 和 SPARC 小鼠在结构参数和生物力学特性方面的性别差异。对性别差异的研究可以帮助提供个性化的治疗方案,更准确地满足患者的需求。

相似文献

1
Exercise improves load bearing bone structural properties in female secreted protein acidic and rich in cysteine (SPARC) null mice but not in males.运动改善雌性分泌型富含半胱氨酸酸性蛋白(SPARC)基因缺失小鼠的承重骨结构特性,但对雄性无影响。
J Orthop Res. 2024 Dec;42(12):2725-2734. doi: 10.1002/jor.25950. Epub 2024 Aug 6.
2
Osteopenia in Sparc (osteonectin)-deficient mice: characterization of phenotypic determinants of femoral strength and changes in gene expression.骨连接蛋白(Sparc)缺乏小鼠的骨质减少:股骨强度表型决定因素及基因表达变化的特征分析
Physiol Genomics. 2007 Dec 19;32(1):64-73. doi: 10.1152/physiolgenomics.00151.2007. Epub 2007 Sep 18.
3
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Secreted protein acidic and rich in cysteine (SPARC) improves glucose tolerance AMP-activated protein kinase activation.富含半胱氨酸的酸性分泌蛋白 (SPARC) 可改善葡萄糖耐量并激活 AMP 激活的蛋白激酶。
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Voluntary running attenuates behavioural signs of low back pain: dimorphic regulation of intervertebral disc inflammation in male and female SPARC-null mice.自愿跑步可减轻腰背痛的行为症状:缺失型丝氨酸蛋白酶抑制因子相关的卷曲蛋白(SPARC)基因敲除雄性和雌性小鼠椎间盘炎症的二态性调节。
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本文引用的文献

1
Secreted Protein Acidic and Rich in Cysteine () KO Leads to an Accelerated Ageing Phenotype Which Is Improved by Exercise Whereas SPARC Overexpression Mimics Exercise Effects in Mice.富含半胱氨酸的酸性分泌蛋白(SPARC)基因敲除导致加速衰老表型,而运动可改善这种表型,而在小鼠中SPARC过表达可模拟运动效果。
Metabolites. 2022 Jan 28;12(2):125. doi: 10.3390/metabo12020125.
2
Measuring Exercise-Induced Secreted Protein Acidic and Rich in Cysteine Expression as a Molecular Tool to Optimize Personalized Medicine.测量运动诱导的分泌蛋白酸性和富含半胱氨酸的表达作为优化个体化医学的分子工具。
Genes (Basel). 2021 Nov 20;12(11):1832. doi: 10.3390/genes12111832.
3
Effect of voluntary running activity on mRNA expression of extracellular matrix genes in a mouse model of intervertebral disc degeneration.
自愿跑步活动对椎间盘退变小鼠模型细胞外基质基因mRNA表达的影响。
JOR Spine. 2021 May 5;4(3):e1148. doi: 10.1002/jsp2.1148. eCollection 2021 Sep.
4
Voluntary running attenuates behavioural signs of low back pain: dimorphic regulation of intervertebral disc inflammation in male and female SPARC-null mice.自愿跑步可减轻腰背痛的行为症状:缺失型丝氨酸蛋白酶抑制因子相关的卷曲蛋白(SPARC)基因敲除雄性和雌性小鼠椎间盘炎症的二态性调节。
Osteoarthritis Cartilage. 2022 Jan;30(1):110-123. doi: 10.1016/j.joca.2021.06.014. Epub 2021 Sep 14.
5
Physical Activity and Bone Vascularization: A Way to Explore in Bone Repair Context?身体活动与骨血管生成:在骨修复背景下的一种探索途径?
Life (Basel). 2021 Aug 2;11(8):783. doi: 10.3390/life11080783.
6
Exercise attenuates low back pain and alters epigenetic regulation in intervertebral discs in a mouse model.运动可减轻小鼠模型的下腰痛,并改变椎间盘的表观遗传调控。
Spine J. 2021 Nov;21(11):1938-1949. doi: 10.1016/j.spinee.2021.06.002. Epub 2021 Jun 9.
7
Exercise-Induced Myokines can Explain the Importance of Physical Activity in the Elderly: An Overview.运动诱导的肌动蛋白可以解释体育活动在老年人中的重要性:综述。
Healthcare (Basel). 2020 Oct 1;8(4):378. doi: 10.3390/healthcare8040378.
8
Biallelic variants in four genes underlying recessive osteogenesis imperfecta.导致隐性成骨不全的四个基因中的双等位基因变异。
Eur J Med Genet. 2020 Aug;63(8):103954. doi: 10.1016/j.ejmg.2020.103954. Epub 2020 May 13.
9
Secreted protein acidic and rich in cysteine (SPARC) improves glucose tolerance AMP-activated protein kinase activation.富含半胱氨酸的酸性分泌蛋白 (SPARC) 可改善葡萄糖耐量并激活 AMP 激活的蛋白激酶。
FASEB J. 2019 Sep;33(9):10551-10562. doi: 10.1096/fj.201900453R. Epub 2019 Jun 21.
10
Interleukin-8 as a therapeutic target for chronic low back pain: Upregulation in human cerebrospinal fluid and pre-clinical validation with chronic reparixin in the SPARC-null mouse model.白细胞介素-8 作为慢性下腰痛的治疗靶点:人脑脊液中的上调和 SPARC 基因缺失小鼠模型中慢性瑞派昔布的临床前验证。
EBioMedicine. 2019 May;43:487-500. doi: 10.1016/j.ebiom.2019.04.032. Epub 2019 Apr 30.