Use of magnetic capture to identify elevated levels of CCL2 following intra-articular injection of monoiodoacetate in rats

Yarmola, Elena G.; Shah, Yash; Lakes, Emily H.; Pacheco, Yan C; Xie, Danny; Dobson, Jon; Allen, Kyle D.

doi:10.1080/03008207.2019.1620223

Cited by 8 publications

(13 citation statements)

References 43 publications

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“…Thus, any effects related to IDO-Gal3 delivery were not detectable in our statistical analyses. While we have previously detected elevated CCL2 and CTXII levels in rodent OA models (27,29), this was in untreated animals and saline injection may have reduced effect sizes to some degree. Nonetheless, IDO-Gal3 did affect IL6 levels at 4 weeks after injection, demonstrating potential to provide sustained effects on OAassociated inflammation.…”

Section: Discussioncontrasting

confidence: 60%

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Intra-Articular Delivery of an Indoleamine 2,3-Dioxygenase Galectin-3 Fusion Protein for Osteoarthritis Treatment in Male Lewis Rats

Partain

Bracho‐Sanchez

Farhadi

et al. 2021

Preprint

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Objective: Controlling joint inflammation can improve osteoarthritis (OA) symptoms; however, current treatments often fail to provide long-term effects. We have developed an indoleamine 2,3-dioxygenase and galectin-3 fusion protein (IDO-Gal3). IDO converts tryptophan to kynurenines, directing the local environment toward an anti-inflammatory state; Gal3 binds carbohydrates and extends IDO's joint residence time. In this study, we evaluated IDO-Gal3's ability to alter OA-associated inflammation and pain-related behaviors in a rat model of established knee OA. Methods: Joint residence was first evaluated with an analog Gal3 fusion protein (NanoLuc and Gal3, NL-Gal3) that produces luminescence from furimazine. OA was induced in male Lewis rats via a medial collateral ligament and medial meniscus transection (MCLT+MMT). At 8 weeks, NL or NL-Gal3 were injected intra-articularly (n=8 per group), and bioluminescence was tracked for 4 weeks. Next, IDO-Gal3's ability to modulate OA pain and inflammation was assessed. Again, OA was induced via MCLT+MMT in male Lewis rats, with IDO-Gal3 or saline injected into OA-affected knees at 8 weeks post-surgery (n=7 per group). Gait and tactile sensitivity were then assessed weekly. At 12 weeks, intra-articular levels of IL6, CCL2, and CTXII were assessed. Results: The Gal3 fusion increased joint residence in OA and contralateral knees (p<0.0001). In OA-affected animals, IDO-Gal3 improved tactile sensitivity (p=0.002), increased walking velocities (p<0.033), and improved vertical ground reaction forces (p<0.04). Finally, IDO-Gal3 decreased intra-articular IL6 levels within the OA-affected joint (p=0.0025). Conclusion: Intra-articular IDO-Gal3 delivery provided long-term modulation of joint inflammation and pain-related behaviors in rats with established OA.

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Section: Discussioncontrasting

confidence: 60%

“…CCL2 was quantified using a rat CCL2 ELISA (Cat. # KRC1012 Life Technologies, Carlsbad, CA, USA) according to manufacturer's instructions and buffer modifications described in Yarmola et al (29). IL6 was quantified using an ELISA developed from an antibody pair (biotin anti-rat IL6 detection antibody, cat.…”

Section: Magnetic Capturementioning

confidence: 99%

Intra-Articular Delivery of an Indoleamine 2,3-Dioxygenase Galectin-3 Fusion Protein for Osteoarthritis Treatment in Male Lewis Rats

Partain

Bracho‐Sanchez

Farhadi

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…CCL2 was quanti ed using a rat CCL2 ELISA (Cat. # KRC1012 Life Technologies, Carlsbad, CA, USA) according to manufacturer's instructions and buffer modi cations described in Yarmola et al (29). IL6 was quanti ed using an ELISA developed from an antibody pair (biotin anti-rat IL6 detection antibody, cat.…”

Section: Magnetic Capturementioning

confidence: 99%

Intra-Articular Delivery of an Indoleamine 2,3-Dioxygenase Galectin-3 Fusion Protein for Osteoarthritis Treatment in Male Lewis Rats

Partain

Bracho‐Sanchez

Farhadi

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Objective: Controlling joint inflammation can improve osteoarthritis (OA) symptoms; however, current treatments often fail to provide long-term effects. We have developed an indoleamine 2,3-dioxygenase and galectin-3 fusion protein (IDO-Gal3). IDO converts tryptophan to kynurenines, directing the local environment toward an anti-inflammatory state; Gal3 binds carbohydrates and extends IDO’s joint residence time. In this study, we evaluated IDO-Gal3’s ability to alter OA-associated inflammation and pain-related behaviors in a rat model of established knee OA. Methods: Joint residence was first evaluated with an analog Gal3 fusion protein (NanoLuc™ and Gal3, NL-Gal3) that produces luminescence from furimazine. OA was induced in male Lewis rats via a medial collateral ligament and medial meniscus transection (MCLT+MMT). At 8 weeks, NL or NL-Gal3 were injected intra-articularly (n=8 per group), and bioluminescence was tracked for 4 weeks. Next, IDO-Gal3’s ability to modulate OA pain and inflammation was assessed. Again, OA was induced via MCLT+MMT in male Lewis rats, with IDO-Gal3 or saline injected into OA-affected knees at 8 weeks post-surgery (n=7 per group). Gait and tactile sensitivity were then assessed weekly. At 12 weeks, intra-articular levels of IL6, CCL2, and CTXII were assessed. Results: The Gal3 fusion increased joint residence in OA and contralateral knees (p<0.0001). In OA-affected animals, IDO-Gal3 improved tactile sensitivity (p=0.002), increased walking velocities (p≤0.033), and improved vertical ground reaction forces (p≤0.04). Finally, IDO-Gal3 decreased intra-articular IL6 levels within the OA-affected joint (p=0.0025). Conclusion: Intra-articular IDO-Gal3 delivery provided long-term modulation of joint inflammation and pain-related behaviors in rats with established OA.

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“…Taken together these data indicate that the CX3CL1/CX3CR1 axis predominates in recruitment and pro-inflammatory activation of Ly6C low monocytes in the context of OA initiation. 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: Signals and Cellular Interactions Shaping Monocytes And Macrophages In Ptoamentioning

confidence: 99%

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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Use of magnetic capture to identify elevated levels of CCL2 following intra-articular injection of monoiodoacetate in rats

Cited by 8 publications

References 43 publications

Intra-Articular Delivery of an Indoleamine 2,3-Dioxygenase Galectin-3 Fusion Protein for Osteoarthritis Treatment in Male Lewis Rats

Intra-Articular Delivery of an Indoleamine 2,3-Dioxygenase Galectin-3 Fusion Protein for Osteoarthritis Treatment in Male Lewis Rats

Intra-Articular Delivery of an Indoleamine 2,3-Dioxygenase Galectin-3 Fusion Protein for Osteoarthritis Treatment in Male Lewis Rats

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

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