Associations of plasma YKL-40 concentrations with heel ultrasound parameters and bone turnover markers in the general adult population

Steinke, Jörn; Samietz, Stefanie; Friedrich, Nele; Weiß, Stefan; Michalik, Stephan; Biffar, Reiner; Nauck, Matthias; Völker, Uwe; Wallaschofski, Henri; Pietzner, Maik; Hannemann, Anke

doi:10.1016/j.bone.2020.115675

Cited by 3 publications

(1 citation statement)

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“…Chitinase 3-like 1 (CHI3L1, also known as YKL-40) is a proinflammatory glycoprotein biomarker that has been linked to tissue remodeling and bone resorption. 12 CHI3L1 is secreted by macrophages, synoviocytes, and chondrocytes, 13–16 and can be detected at increased levels in the synovial fluid and serum of patients with inflammatory conditions, in addition to correlating with the extent of joint degradation in rheumatoid arthritis (RA) patients. 17 Inhibiting CHI3L1 has previously been shown to suppress inflammation and cortical bone degeneration in a murine osteomyelitis model system, 18 while Kim et al 19 similarly determined that knocking down this glycoprotein protected against hyperoxia-induced apoptotic death in human airway epithelial cells, whereas CHI3L1 overexpression increased the susceptibility of these cells to such apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Nrf2 Regulates CHI3L1 to Suppress Inflammation and Improve Post-Traumatic Osteoarthritis

Song¹,

Hao²,

Jiang³

et al. 2021

JIR

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Introduction: Post-traumatic osteoarthritis (PTOA) is an inflammatory condition that occurs following mechanical joint trauma and that results in joint degeneration. This study sought to evaluate the regulatory function of nuclear factor erythroid 2-related factor 2 (Nrf2) in a murine model of anterior cruciate ligament transection (ACLT)-induced PTOA and in an in vitro model of synoviocyte inflammation induced by LPS treatment with the goal of exploring the role of chitinase 3-like-1 (CHI3L1) in this pathogenic context. Methods: PTOA model mice were intra-articularly injected with Nrf2 overexpression lentiviral vector, and safranin O-fast green staining as well as the Osteoarthritis Research Society International (OARSI) Scoring System were used to evaluate the severity of cartilage damage. Protein expression in the synovial tissue was evaluated by Western blotting, immunohistochemical staining, and ELISA. Additionally, murine synoviocytes were infected with Nrf2 overexpression lentivirus and stimulated with LPS. The levels of inflammatory cytokines were detected by ELISA. ROS levels were measured using dihydroethidium (DHE) dye. Results: We determined that the overexpression of Nrf2 was sufficient to reduce cartilage degradation in the context of PTOA in vivo, and we observed a significant decrease in the expression of matrix metalloproteinase 13 (MMP13) in the articular cartilage of samples from mice overexpressing Nrf2 relative to control mice. Synovial CHI3L1 expression and serum TNF-α, IL-1β, and IL-6 levels were reduced in animals overexpressing this transcription factor relative to PTOA model controls. Consistent with these findings, murine synoviocytes treated with LPS exhibited dose-dependent increases in ROS, TNF-α, IL-1β, IL-6, Nrf2, and CHI3L1 levels, whereas Nrf2 overexpression was sufficient to suppress these increases. Conclusion:Our data indicated that Nrf2 negatively regulates CHI3L1, suggesting that this signaling axis may regulate PTOA progression and may thus be a viable therapeutic target in individuals affected by this condition.

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