The subchondral bone is an emerging regulator of osteoarthritis (OA). However, knowledge of how specific subchondral alterations relate to cartilage degeneration remains incomplete. Femoral heads were obtained from 44 patients with primary OA during total hip arthroplasty and from 30 non-OA controls during autopsy. A multiscale assessment of the central subchondral bone region comprising histomorphometry, quantitative backscattered electron imaging, nanoindentation, and osteocyte lacunocanalicular network characterization was employed. In hip OA, thickening of the subchondral bone coincided with a higher number of osteoblasts (controls: 3.7 ± 4.5 mm, OA: 16.4 ± 10.2 mm, age-adjusted mean difference 10.5 mm [95% CI 4.7 to 16.4], < 0.001) but a similar number of osteoclasts compared to controls ( = 0.150). Furthermore, higher matrix mineralization heterogeneity (CaWidth, controls: 2.8 ± 0.2 wt%, OA: 3.1 ± 0.3 wt%, age-adjusted mean difference 0.2 wt% [95% CI 0.1 to 0.4], = 0.011) and lower tissue hardness (controls: 0.69 ± 0.06 GPa, OA: 0.67 ± 0.06 GPa, age-adjusted mean difference −0.05 GPa [95% CI −0.09 to −0.01], = 0.032) were detected. While no evidence of altered osteocytic perilacunar/canalicular remodeling in terms of fewer osteocyte canaliculi was found in OA, specimens with advanced cartilage degeneration showed a higher number of osteocyte canaliculi and larger lacunocanalicular network area compared to those with low-grade cartilage degeneration. Multiple linear regression models indicated that several subchondral bone properties, especially osteoblast and osteocyte parameters, were closely related to cartilage degeneration (R adjusted = 0.561, < 0.001). Subchondral bone properties in OA are affected at the compositional, mechanical, and cellular levels. Based on their strong interaction with cartilage degeneration, targeting osteoblasts/osteocytes may be a promising therapeutic OA approach. All data are available in the main text or the supplementary materials.

中文翻译：

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软骨下骨成分和细胞特性的改变与髋骨关节炎中的软骨退化有关

软骨下骨是骨关节炎（OA）的新兴调节因子。然而，关于特定软骨下改变如何与软骨退化相关的知识仍然不完整。股骨头取自全髋关节置换术期间的 44 名原发性 OA 患者和尸检期间的 30 名非 OA 对照患者。采用了对中央软骨下骨区域的多尺度评估，包括组织形态计量学、定量背散射电子成像、纳米压痕和骨细胞腔隙小管网络表征。在髋部 OA 中，软骨下骨增厚与成骨细胞数量增加一致（对照：3.7 ± 4.5 mm，OA：16.4 ± 10.2 mm，年龄调整平均差 10.5 mm [95% CI 4.7 至 16.4]，< 0.001）但与对照组相比，破骨细胞数量相似 (= 0.150)。此外，更高的基质矿化异质性（CaWidth，对照：2.8 ± 0.2 wt%，OA：3.1 ± 0.3 wt%，年龄调整平均差异 0.2 wt% [95% CI 0.1 至 0.4]，= 0.011）和较低的组织硬度（检测到对照组：0.69 ± 0.06 GPa，OA：0.67 ± 0.06 GPa，年龄调整平均差 -0.05 GPa [95% CI -0.09 至 -0.01]，= 0.032）。虽然在 OA 中没有发现骨细胞小管周围/小管重塑发生改变的证据，但与低度软骨退变的标本相比，晚期软骨退变的标本显示出更多的骨细胞小管数量和更大的空腔小管网络面积。多元线性回归模型表明，多种软骨下骨特性，尤其是成骨细胞和骨细胞参数，与软骨退变密切相关（调整后的R = 0.561，<0.001）。骨关节炎的软骨下骨特性在成分、机械和细胞水平上受到影响。基于它们与软骨退变的强烈相互作用，靶向成骨细胞/骨细胞可能是一种有前途的骨关节炎治疗方法。所有数据都可以在正文或补充材料中找到。