Transient anabolic effects of synovium in early post-traumatic osteoarthritis: a novel ex vivo joint tissue co-culture system for investigating synovium-chondrocyte interactions

Lai-Zhao, Yue; Pitchers, Kyle K.; Appleton, T.

doi:10.1016/j.joca.2021.03.010

Cited by 8 publications

(25 citation statements)

References 43 publications

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“…Together these data are consistent with clinical signs of osteoarthritis such as synovitis and cartilage degeneration. 1,2,23 The synovium plays a key role in maintaining joint homeostasis, lubricating the joint and facilitating the flow of synovial fluid therein. 26 Herein, we observed clear signs of synovial fibrosis in ACLT model mice, consistent with the impairment of synovial function.…”

Section: Discussionmentioning

confidence: 99%

“…PTOA is a form of osteoarthritis (OA), a chronic disease that can cause synovial joint pain and even disability in severe cases. 23 The knee is the most common site of traumatic synovitis in the body. 24 Herein, we utilized a murine model of PTOA via conducting ACLT of the right knee joint.…”

Section: Discussionmentioning

confidence: 99%

“…Together these data are consistent with clinical signs of osteoarthritis such as synovitis and cartilage degeneration. 1 , 2 , 23 …”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Song¹,

Hao²,

Jiang³

et al. 2021

JIR

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“…Ly6C high monocytes recruited and activated via CCL2/CCR2, on the other hand, might help sustain inflammation at later stages (192). Temporal changes in chemokine expression and associated monocyte sub-population recruitment and accumulation, may in part explain the recently described loss with time post-injury, of an initially protective/ anabolic effect of injured synovium on chondrocytes (193).…”

Section: Mechanisms Underlying Monocyte Recruitment During Oa Pathogenesismentioning

confidence: 97%

Monocytes, Macrophages, and Their Potential Niches in Synovial Joints – Therapeutic Targets in Post-Traumatic Osteoarthritis?

et al. 2021

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Synovial joints are complex structures that enable normal locomotion. Following injury, they undergo a series of changes, including a prevalent inflammatory response. This increases the risk for development of osteoarthritis (OA), the most common joint disorder. In healthy joints, macrophages are the predominant immune cells. They regulate bone turnover, constantly scavenge debris from the joint cavity and, together with synovial fibroblasts, form a protective barrier. Macrophages thus work in concert with the non-hematopoietic stroma. In turn, the stroma provides a scaffold as well as molecular signals for macrophage survival and functional imprinting: “a macrophage niche”. These intricate cellular interactions are susceptible to perturbations like those induced by joint injury. With this review, we explore how the concepts of local tissue niches apply to synovial joints. We introduce the joint micro-anatomy and cellular players, and discuss their potential interactions in healthy joints, with an emphasis on molecular cues underlying their crosstalk and relevance to joint functionality. We then consider how these interactions are perturbed by joint injury and how they may contribute to OA pathogenesis. We conclude by discussing how understanding these changes might help identify novel therapeutic avenues with the potential of restoring joint function and reducing post-traumatic OA risk.

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“…In an elegant study where healthy rat chondrocytes were co-cultured with synovium harvested at different time points after OA induction, addition of synovium initially showed higher aggrecan production of the chondrocytes, suggesting injury induced a transient anabolic effect. With increased OA stage of the isolated synovium, however, this changed into an increase of monocyte chemoattractant protein 1 (MCP-1), a chemokine initiating inflammation ( Xu et al, 2015 ; Lai-Zhao et al, 2021 ). The effects did not seem to be related to the OA induction surgery, but rather the injury of the joint, as similar results were observed using synovium from sham surgery controls ( Lai-Zhao et al, 2021 ).…”

Section: Co-cultured Tissue Explantsmentioning

confidence: 99%

The Added Value of the “Co” in Co-Culture Systems in Research on Osteoarthritis Pathology and Treatment Development

Muenzebrock

Kersten

Alblas

et al. 2022

Front. Bioeng. Biotechnol.

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Osteoarthritis (OA) is a highly prevalent disease and a major health burden. Its development and progression are influenced by factors such as age, obesity or joint overuse. As a whole organ disease OA affects not only cartilage, bone and synovium but also ligaments, fatty or nervous tissue surrounding the joint. These joint tissues interact with each other and understanding this interaction is important in developing novel treatments. To incorporate and study these interactions in OA research, several co-culture models have evolved. They combine two or more cell types or tissues and investigate the influence of amongst others inflammatory or degenerative stimuli seen in OA. This review focuses on co-cultures and the differential processes occurring in a given tissue or cell as a consequence of being combined with another joint cell type or tissue, and/or the extent to which a co-culture mimics the in vivo processes. Most co-culture models depart from synovial lining and cartilage culture, but also fat pad and bone have been included. Not all of the models appear to reflect the postulated in vivo OA pathophysiology, although some of the discrepancies may indicate current assumptions on this process are not entirely valid. Systematic analysis of the mutual influence the separate compartments in a given model exert on each other and validation against in vivo or ex vivo observation is still largely lacking and would increase their added value as in vitro OA models.

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Transient anabolic effects of synovium in early post-traumatic osteoarthritis: a novel ex vivo joint tissue co-culture system for investigating synovium-chondrocyte interactions

Cited by 8 publications

References 43 publications

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

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

Monocytes, Macrophages, and Their Potential Niches in Synovial Joints – Therapeutic Targets in Post-Traumatic Osteoarthritis?

The Added Value of the “Co” in Co-Culture Systems in Research on Osteoarthritis Pathology and Treatment Development

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