Endothelin-1 inhibits size dependent lymphatic clearance of PEG-based conjugates after intra-articular injection into the rat knee

Doan, Thanh N.; Bernard, Fabrice C; McKinney, Jay M.; Dixon, J. Brandon; Willett, Nick J.

doi:10.1016/j.actbio.2019.04.025

Cited by 33 publications

(26 citation statements)

References 67 publications

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“…Unlike intradermal injections, materials from the joint space clear much slower [29][30][31] ; therefore, venous and lymphatic clearance from this interstitial depot was expected to occur over one day. Simultaneously injected tracer clearance PEG and free dye profiles (Figure 4a) exhibited an initial increase followed by monoexponential clearance kinetics consistent with previously reported figures 23 . Specifically, lymphatic tracers showed a more substantial increase in intensity after the injection, whereas this increase was less pronounced for the venous tracer.…”

Section: Co-injection To Assess Differential Tracer Clearance In the Jointsupporting

confidence: 88%

“…We have previously shown the size-dependent uptake of and 40 kDa NIR PEG into the venous and lymphatic circulation, respectively, after injection into the rat knee joint 23 . In that study, we demonstrated that the intra-articular injection of endothelin-1 (ET-1), a vasoactive compound in lymphatics and veins, transiently reduced the outflow of both PEG tracers from the joint in a dose-dependent manner.…”

Section: Introductionmentioning

confidence: 96%

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Multichromatic Near-Infrared Imaging to Assess Interstitial Lymphatic and Venous UptakeIn Vivo

Kaiser

et al. 2021

Preprint

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Significance: Changes in interstitial fluid clearance are implicated in many diseases. Using NIR imaging with properly sized tracers could enhance our understanding of how venous and lymphatic drainage are involved in disease progression or enhance drug delivery strategies. Aim: We investigated multichromatic NIR imaging with multiple tracers to assess in vivo microvascular clearance kinetics and pathways in different tissue spaces. Approach: We used a chemically inert IR Dye 800CW (free dye) to target venous capillaries and a purified conjugate of IR Dye 680RD with a 40 kDa PEG (PEG) to target lymphatic capillaries in vivo. Optical imaging settings were validated and tuned in vitro using tissue phantoms. We investigated multichromatic NIR imaging's utility in two in vivo tissue beds, the mouse tail and rat knee joint. We then tested the ability of the approach to detect interstitial fluid perturbations due to exercise. Results: In an in vitro simulated tissue environment, free dye and PEG mixture allowed for simultaneous detection without interference. Co-injected NIR tracers cleared from the interstitial space via distinct routes allowed assessment lymphatic and venous uptake in the mouse tail. We determined that exercise after injection transiently increased lymphatic drainage as measured by

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Section: Co-injection To Assess Differential Tracer Clearance In the Jointsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 96%

Multichromatic Near-Infrared Imaging to Assess Interstitial Lymphatic and Venous UptakeIn Vivo

Kaiser

et al. 2021

Preprint

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“…Others have reported a modest protective effect of local NF-κB inhibition on both the histological development of PTOA and hyperalgesia following a less severe, non-instability inducing, mechanical joint injury 13,45 . For these reasons, future work should seek to increase the duration of drug presence within the joint following injury either via increased dosing frequency or with sustained release formulations [46][47][48][49] .…”

Section: Discussionmentioning

confidence: 99%

NF-κB-mediated effects on behavior and cartilage pathology in a non-invasive loading model of post-traumatic osteoarthritis

Berke

Jain

Yavuz

et al. 2021

Osteoarthritis and Cartilage

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“…The striking effect of SF, both OASF (OASF-pool and OASF#3) and HSF, on the tonic and phasic lymphatic contractions serves as a further indication of the importance of the lymphatic system in the concept of OA (Wilkinson and Edwards, 1991;Yoshida et al, 1997;Bouta et al, 2015;Simkin, 2015;Doan et al, 2019). A potential use of SF as a means of therapeutic for OA should be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Effect of human synovial fluid from osteoarthritis patients and healthy individuals on lymphatic contractility

Michalaki

Nepiyushchikh

Bernard

et al. 2020

Preprint

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The lymphatic system has been proposed to play a crucial role in the development and progression of osteoarthritis (OA). The synovial fluid (SF) of arthritic joints contains mediators of the inflammatory response and products of the injury to articular tissues, while lymphatic system plays a critical role in resolving inflammation and overall joint homeostasis. Despite the importance of both the lymphatic system and SF in OA disease, their relationship is still poorly understood. Here, we utilized SF derived from osteoarthritis patients (OASF) and healthy individuals (HSF) to investigate potential effects of SF on migration of lymphatic endothelial cells (LECs) in vitro, and lymphatic contractility of femoral lymphatic vessels (LVs) ex vivo. Both OASF and HSF treatments led to an increased migratory response in vitro compared to LECs treatment with media without serum. Ex vivo, both OASF and HSF treatments to the lumen of isolated LVs led to significant differences in the tonic and phasic contractions and these observations were dependent on the SF treatment time. Specifically, OASF treatment transiently enhanced the RFLVs tonic contractions. Regarding the phasic contractions, OASF generated either an abrupt reduction after 1 hr of treatment or a complete cease of contractions after an overnight treatment, while HSF treatment displayed a gradual decrease in lymphatic contractility. The observed variations after SF treatments suggest that the pump function of lymphatic vessel draining the joint could be directly compromised in OA and thus might present a new therapeutic target.

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Endothelin-1 inhibits size dependent lymphatic clearance of PEG-based conjugates after intra-articular injection into the rat knee

Cited by 33 publications

References 67 publications

Multichromatic Near-Infrared Imaging to Assess Interstitial Lymphatic and Venous UptakeIn Vivo

Multichromatic Near-Infrared Imaging to Assess Interstitial Lymphatic and Venous UptakeIn Vivo

NF-κB-mediated effects on behavior and cartilage pathology in a non-invasive loading model of post-traumatic osteoarthritis

Effect of human synovial fluid from osteoarthritis patients and healthy individuals on lymphatic contractility

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