Blocking of checkpoint receptor PD-L1 aggravates osteoarthritis in macrophage-dependent manner in the mice model

Abstract

As a chronic degenerative joint disease, osteoarthritis is among the most common diseases all over the world. In osteoarthritis, inflammation plays an important role in the generation of joint symptoms and the development of disease. When the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint is blocked, the antitumor immunity will be enhanced. We aim to illustrate the function of PD-L1 in osteoarthritis. Osteoarthritis in mice was induced by the injection of collagenase or anterior cruciate ligament transection (ACLT). Anti-PD-L1 was employed to block the signal of PD-L1. Knee joints histological sections were stained by Safranin-O. The level of cytokine was checked by enzyme-linked immunosorbent assay (ELISA) and mRNA level was shown by quantitative reverse transcriptase polymerase chain reaction. The blockade of PD-L1 signal up-regulated inflammatory response and promoted the development of osteoarthritis in mice. The inflammatory cytokine interleukin-6 and tumor necrosis factor-α expression were promoted by PD-L1 blocking in macrophages. Osteoarthritis was aggravated when the expression of inflammatory cytokine is elevated in macrophages. Our results indicated that the blockade of PD-L1 signal in macrophages elevates the expression of inflammatory cytokine and promotes the development of osteoarthritis in mice, which could be utilized as a potential diagnostic and therapeutic target for osteoarthritis patients.

Cepharanthine: An update of its mode of action, pharmacological properties and medical applications

“…CEP would not repair the already degraded cartilage, but the drug might avoid damage extension to the surrounding tissue, by limiting the production of pro-inflammatory cytokines and chemokines (Herrero-Beaumont et al, 2019). In particular, osteoarthritis patients suffering from a cancer and treated with a regulator of the PD1/PDL1 immune checkpoint might face an aggravation of their osteoarthritis due to a treatment-induced elevated expression of inflammatory cytokine in macrophages (Liu et al, 2019). The use of CEP might thus be Fig.…”

Bone fracture as a novel immune‐related adverse event with immune checkpoint inhibitors: Case series and large‐scale pharmacovigilance analysis

“…Emerging evidence suggests that systemic activation of T cells in vivo leads to an osteoprotegerin ligand-mediated increase in osteoclastogenesis and bone loss (Figure 1). In fact, ICIs can enhance bone resorption by activating T cells, 8 which in turn causes bone loss with bone fragility, increasing the risk of fractures. 9,10 In the recent past, the Food and Drug Administration Adverse Event Reporting System (FAERS) has attracted considerable interest among clinicians for accurate and timely characterization of drugrelated risks occurring in real-world cancer patients with comorbidities and polypharmacotherapy.…”

Inhibition of microRNA‐27b‐3p relieves osteoarthritis pain via regulation of KDM4B‐dependent DLX5

“…OA represents a long-term degenerative joint disease characterized by inflammation resulting in the formation of joint symptoms and progression of the disease. 25,26 Pain is the classical symptom experienced by patients suffering from OA as well as the dominant factor influencing the health professional's decision in terms of pain management. 27 More recently, research studies have highlighted the involvement of miRNAs in the development of OA.…”