Deletion of Hyaluronan-Binding Protein Involved in Hyaluronan Depolymerization (HYBID) Results in Attenuation of Osteoarthritis in Mice
Deletion of Hyaluronan-Binding Protein Involved in Hyaluronan Depolymerization (HYBID) Results in Attenuation of Osteoarthritis in Mice
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DOI：
10.1016/j.ajpath.2021.07.008
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发表时间：
2021-10-25
影响因子：
6
通讯作者：
Okada, Yasunori
中科院分区：
文献类型：
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作者：
Momoeda, Masahiro;de Vega, Susana;Okada, Yasunori
透明质酸结合蛋白参与了透明质酸解聚(HYBID)，参与了人膝关节骨关节炎中透明质酸解聚对软骨的破坏。然而，混浊在骨性关节炎进展中的作用仍然难以捉摸。这项研究试图检验杂多酸的基因缺失是否可以抑制手术诱导的小鼠膝关节骨关节炎。在半月板切除内侧副韧带切断所致的骨性关节炎中，与野生型小鼠相比，高水分缺乏(-/-)小鼠的股骨-胫骨内侧关节软骨的破坏和骨赘的形成明显受到抑制。野生型小鼠骨关节炎关节滑膜细胞和关节软骨细胞产生大量的杂化物。IL-1b、IL-6和肿瘤坏死因子-a在野生型和杂合型(-/-)小鼠骨关节炎关节组织中均上调。与野生型小鼠相比，杂合型(-/-)小鼠滑膜和骨膜交界处的血管密度显著降低。HYBID(-/-)小鼠骨关节炎关节组织中高相对分子质量HA蓄积。膝关节注射高分子羟基磷灰石可减轻野生型小鼠骨关节炎软骨破坏和骨赘形成。在内侧半月板模型的失稳中，也观察到抑制高(-/-)小鼠的软骨破坏和骨赘形成。这些数据首次证明了杂音(-/-)小鼠的软骨破坏和骨赘形成受到抑制，并提示杂音介导的HA解聚与机械性膝骨性关节炎的进展有关。(Am J Pathol2021年，191年：1986年-1998年；https://doi.org/10.1016/j.ajpath.2021.07.008)
Hyaluronan (HA)-binding protein involved in HA depolymerization (HYBID) is involved in cartilage destruction via HA depolymerization in human knee osteoarthritis. However, the role of HYBID in the progression of osteoarthritis remain elusive. This study sought to examine whether genetic depletion of Hybid could suppress surgically induced osteoarthritis of mouse knee joints. In osteoarthritis induced by medial collateral ligament transection with meniscus removal, articular cartilage destruction and osteophyte formation at the medial femoral-tibial joint were significantly inhibited in Hybid-deficient (Hybid(-/-)) mice compared with wild-type mice. Hybid was highly produced by synovial cells and articular chondrocytes in the osteoarthritis joints of wild-type mice. IL-1b, IL-6, and tumor necrosis factor-a were up-regulated in the osteoarthritis joint tissues of both wild-type and Hybid(-/-) mice. Vascular density at the synovial and periosteal junction was significantly reduced in Hybid(-/-) mice compared with wild-type mice. High-molecular-weight HA accumulated in osteoarthritis joint tissues of Hybid(-/-)mice. Injections of high-molecular-weight HA to knee joints attenuated the cartilage destruction and osteophyte formation in wild-type mouse osteoarthritis group. Inhibition of cartilage destruction and osteophyte formation in Hybid(-/-) mice was also observed in destabilization of the medial meniscus model. These data are the first to demonstrate that cartilage destruction and osteophyte formation are suppressed in Hybid(-/-) mice and suggest that Hybid-mediated HA depolymerization is implicated for the progression of mechanically-induced knee osteoarthritis. (Am J Pathol 2021, 191: 1986-1998; https://doi.org/10.1016/j.ajpath.2021.07.008)