酮体 β-羟丁酸通过调节 NLRP3 炎性小体和破骨细胞分化缓解 CoCrMo 合金颗粒诱导的溶骨作用。
The ketone body β-hydroxybutyrate alleviates CoCrMo alloy particles induced osteolysis by regulating NLRP3 inflammasome and osteoclast differentiation.
机构信息
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China.
Orthopaedic Institute, Medical College, Soochow University, Suzhou, 215007, China.
出版信息
J Nanobiotechnology. 2022 Mar 9;20(1):120. doi: 10.1186/s12951-022-01320-0.
BACKGROUND
Aseptic Loosening (AL) following periprosthetic osteolysis is the main long-term complication after total joint arthroplasty (TJA). However, there is rare effective treatment except for revision surgery, which is costly and painful to the patients. In recent years, the ketone body β-hydroxybutyrate (BHB) has attracted much attention and has been proved to be beneficial in many chronic diseases. With respect to the studies on the ketone body β-hydroxybutyrate (BHB), its anti-inflammatory ability has been widely investigated. Although the ketone body β-hydroxybutyrate has been applied in many inflammatory diseases and has achieved considerable therapeutic efficacy, its effect on wear particles induced osteolysis is still unknown.
RESULTS
In this work, we confirmed that the anti-inflammatory action of β-hydroxybutyrate (BHB) could be reappeared in CoCrMo alloy particles induced osteolysis. Mechanistically, the ketone body β-hydroxybutyrate (BHB) deactivated the activation of NLRP3 inflammasome triggered by CoCrMo alloy particles. Of note, this inhibitory action was independent of Gpr109a receptor as well as histone deacetylase (HDAC) suppression. Furthermore, given that butyrate, one kind of short chain fatty acid (SCFA) structurally related to β-hydroxybutyrate (BHB), has been reported to be an inhibitor of osteoclast, thus we also investigate the effect of β-hydroxybutyrate (BHB) on osteoclast, which was contributed to bone resorption. It was found that β-hydroxybutyrate (BHB) did not only affect osteoclast differentiation, but also inhibit its function. Unlike the inflammasome, the effect of β-hydroxybutyrate (BHB) on osteoclast may mainly rely on histone deacetylase (HDAC) suppression.
CONCLUSIONS
In general, our study showed that the alleviation of osteolysis may owe to the effect of β-hydroxybutyrate (BHB) on inflammasome deactivation and osteoclast.
背景
假体周围骨溶解（AL）是全膝关节置换术后（TJA）的主要长期并发症。然而，除了翻修手术外，目前几乎没有有效的治疗方法，而翻修手术对患者来说既昂贵又痛苦。近年来，酮体β-羟丁酸（BHB）引起了广泛关注，并已被证明对许多慢性疾病有益。关于酮体β-羟丁酸（BHB）的研究，其抗炎能力已被广泛研究。尽管酮体β-羟丁酸已应用于许多炎症性疾病，并取得了相当的治疗效果，但它对磨损颗粒诱导的骨溶解的影响尚不清楚。
结果
在这项工作中，我们证实β-羟丁酸（BHB）的抗炎作用可以在 CoCrMo 合金颗粒诱导的骨溶解中重现。从机制上讲，酮体β-羟丁酸（BHB）可使 CoCrMo 合金颗粒触发的 NLRP3 炎性小体失活。值得注意的是，这种抑制作用不依赖于 Gpr109a 受体和组蛋白去乙酰化酶（HDAC）抑制。此外，鉴于丁酸盐是与β-羟丁酸（BHB）结构相关的短链脂肪酸（SCFA）之一，已报道其是破骨细胞的抑制剂，因此我们还研究了β-羟丁酸（BHB）对破骨细胞的影响，这有助于骨吸收。结果发现，β-羟丁酸（BHB）不仅影响破骨细胞分化，还抑制其功能。与炎性小体不同，β-羟丁酸（BHB）对破骨细胞的作用可能主要依赖于组蛋白去乙酰化酶（HDAC）抑制。
结论
总的来说，我们的研究表明，骨溶解的缓解可能归因于β-羟丁酸（BHB）对炎性小体失活和破骨细胞的作用。
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