Dept. Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver BC, Canada.
School of Engineering and Materials Science, Queen Mary, University of London, London, U.K..
BMC Musculoskelet Disord. 2023 Apr 12;24(1):282. doi: 10.1186/s12891-023-06375-0.
Hypercholesterolemia is associated with tendon pathology, but the reasons underpinning this relationship are not well understood. Cholesterol can accumulate in the tendon non-collagenous matrix which may affect both global and local tissue mechanics. Changes to the local strain environment within tendon may have significant implications for mechanosensitive tenocytes. Here, we investigated the association between elevated blood cholesterol and presence of tendon lipids in the Achilles tendon. We expected lipids to be localised in the proteoglycan-rich inter-sub-tendon matrix (ISTM), therefore we also sought to examine the impact of this on the biomechanical and viscoelastic properties of the ISTM.
The Achilles tendons of 32 young wild-type (SD) and 32 apolipoprotein E knock-out rats (ApoE) were harvested at 15.6 ± 2.3 weeks of age. 32 specimens underwent histological examination to assess the distribution of lipids throughout sub-tendons and ISTM. The remaining specimens were prepared for biomechanical testing, where the ISTM between the gastrocnemius and soleus sub-tendons was subjected to shear load mechanical testing. A sub-set of tests were video recorded to enable a strain analysis.
ApoE serum cholesterol was double that of SD rats (mean 2.25 vs. 1.10 mg/ml, p < 0.001) indicating a relatively mild hypercholesterolemia phenotype. Nonetheless, we found histological evidence of esterified lipids in the ISTM and unesterified lipids in the sub-tendons, although the location or intensity of staining was not appreciably different between rat strains. Despite a lack of observable histological differences in lipid content between groups, there were significant differences in the mechanical and viscoelastic behaviour of the Achilles sub-tendon matrix.
Even slightly elevated cholesterol may result in subtle changes to tendon biomechanical properties and hence injury risk. The young age of our cohort and the mild phenotype of our ApoE rats are likely to have limited our findings and so we also conclude that the ApoE rat model is not well suited for investigating the biomechanical impact of tendon xanthomas on Achilles sub-tendon function.
高胆固醇血症与肌腱病变有关，但这种关系的潜在原因尚不清楚。胆固醇可在肌腱非胶原基质中蓄积，这可能会影响肌腱的整体和局部组织力学特性。肌腱内局部应变环境的变化可能对机械敏感的腱细胞有重大影响。在这里，我们研究了升高的血胆固醇与跟腱中肌腱脂质的存在之间的关系。我们预计脂质将定位于富含蛋白聚糖的亚肌腱基质（ISTM）中，因此我们还试图研究这种情况对 ISTM 的生物力学和粘弹性特性的影响。
15.6±2.3 周龄时，采集 32 只年轻野生型（SD）和 32 只载脂蛋白 E 敲除大鼠（ApoE）的跟腱。32 个标本进行组织学检查，以评估亚肌腱和 ISTM 中脂质的分布。其余标本用于生物力学测试，其中跟腱的比目鱼肌和腓肠肌亚肌腱之间的 ISTM 受到剪切载荷的机械测试。对一部分测试进行了视频记录，以进行应变分析。
ApoE 血清胆固醇是 SD 大鼠的两倍（平均值 2.25 与 1.10mg/ml，p<0.001），表明存在相对轻度的高胆固醇血症表型。尽管如此，我们在 ISTM 中发现了酯化脂质的组织学证据，在亚肌腱中发现了未酯化脂质，但两种大鼠品系之间的染色位置或强度并无明显差异。尽管组间脂质含量的组织学差异不明显，但跟腱亚肌腱基质的机械和粘弹性行为存在显著差异。
即使胆固醇略有升高，也可能导致肌腱生物力学特性的细微变化，从而增加受伤风险。我们的研究对象年龄较轻，ApoE 大鼠的表型较温和，这可能限制了我们的发现，因此我们还得出结论，ApoE 大鼠模型不太适合研究跟腱亚腱功能的腱黄瘤对跟腱的生物力学影响。
