Weight-bearing asymmetry and vertical activity differences in a rat model of post-traumatic knee osteoarthritis

Hamilton, Clayon B.; Pest, M.A.; Pitelka, V.; Ratneswaran, A.; Beier, Frank; Chesworth, Bert M.

doi:10.1016/j.joca.2015.03.001

Cited by 29 publications

(29 citation statements)

References 42 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Meniscal injuries are highly prevalent and often treated by arthroscopic meniscal debridement or Mx . Mx increases the relative risk for PTOA in humans sixfold and in animal models has been validated to lead to PTOA . The Mx model is used to study biomechanical destabilization and biological changes to the contact surfaces.…”

Section: Surgically Induced Animal Models Of Post‐traumatic Osteoarthmentioning

confidence: 99%

Use of pre‐clinical surgically induced models to understand biomechanical and biological consequences of PTOA development

Barton

Shekarforoush

Heard

et al. 2017

Journal Orthopaedic Research

View full text Add to dashboard Cite

Post-traumatic osteoarthritis (PTOA) development is often observed following traumatic knee injuries involving key stabilising structures such as the cruciate ligaments or the menisci. Both biomechanical and biological alterations that follow knee injuries have been implicated in PTOA development, although it has not been possible to differentiate clearly between the two causal factors. This review critically examines the outcomes from pre-clinical lapine and ovine injury models arising in the authors' laboratories and differing in severity of PTOA development and progression. Specifically, we focus on how varying severity of knee injuries influence the subsequent alterations in kinematics, kinetics, and biological outcomes. The immediate impact of injury on the lubrication capacity of the joint is examined in the context of its influence on biomechanical alterations, thus linking the biological changes to abnormal kinematics, leading to a focus on the potential areas for interventions to inhibit or prevent development of the disease. We believe that PTOA results from altered cartilage surface interactions where biological and biomechanical factors intersect, and mitigating acute joint inflammation may be critical to prolonging PTOA development. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:454-465, 2017.

show abstract

Section: Surgically Induced Animal Models Of Post‐traumatic Osteoarthmentioning

confidence: 99%

Use of pre‐clinical surgically induced models to understand biomechanical and biological consequences of PTOA development

Barton

Shekarforoush

Heard

et al. 2017

Journal Orthopaedic Research

View full text Add to dashboard Cite

show abstract

“…Right knee joints were cut into serial frontal sections (5-µM thick) and stained using 0.04% toluidine blue from six different depths spanning 0.4 µm of the joint. Structural joint changes were assessed using the Osteoarthritis Research Society International for cartilage degeneration score (17). …”

Section: Methodsmentioning

confidence: 99%

Sivelestat sodium hydrate improves post-traumatic knee osteoarthritis through nuclear factor-κB in a rat model

Xiao¹,

Zhao

Yu³

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

As a specific inhibitor of neutrophil elastase, sivelestat sodium hydrate has primarily been used in the treatment of acute lung injury caused by various factors since its approval in 2002. Sivelestat sodium hydrate also improves post-traumatic knee osteoarthritis (KOA), although its underlying mechanisms of action have yet to be elucidated. The aim of the current study was to determine if sivelestat sodium hydrate improves post-traumatic KOA through nuclear factor (NF)-κB in a rat model. Treatment with sivelestat sodium hydrate significantly inhibited the induction of structural changes and significantly increased the vertical episode count and ipsilateral static weight bearing of the joint in KOA rats (all P<0.01). Sivelestat sodium hydrate significantly inhibited tumor necrosis factor-α and interleukin-6 production, serum nitrite levels, inducible nitric oxide synthase protein expression and high mobility group box 1 (HMGB1) secretion in KOA rats compared with the model group (all P<0.01). Sivelestat sodium hydrate also significantly suppressed p50/p65 DNA binding activity and NF-κB and phosphorylated inhibitor of κB protein expression in the joints of KOA rats compared with the model group (all P<0.01). These results suggest that sivelestat sodium hydrate improves post-traumatic KOA through HMGB1 and NF-κB in rats.

show abstract

“…The right knee joint was exposed by incision from the medial side of the patella, and the medial collateral ligament was removed to open the articular cavity. The rats then underwent anterior cruciate ligament transection in combination with partial medial meniscectomy (ACLT + pMMx) on the right knee as described previously (18,19) . Finally, the incisions were sutured and ACLT + pMMx surgeries were induced after complete hemostasis was achieved.…”

Section: Reagentsmentioning

confidence: 99%

Positive Feedback Regulation Between USP15 and ERK2 Promotes Cartilage Repair in Experimental Osteoarthritis

Wang¹,

Zhu²,

Sun³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background.The transforming growth factor-β (TGF-β) signaling pathway plays an essential role in maintaining homeostasis in joints affected by osteoarthritis (OA). Determine the specific relationship between non-SMAD and classical SMAD signaling pathways.Methods.First,we found from human cartilage tissue specimens positive expressions of TGF-β1 and USP15between normal andosteoarthritiscartilage tissueby immunohistochemical.Then, overexpressing and knocking out USP15 or ERK2 followed bythe latest gene editing technology Crispr/Cas9 supported the studyinvitro.And we established rat knee OAmodelsthrough anterior cruciate ligament transection in combination with partial medial meniscectomy (ACLT+pMMx)after 8 weeksand conducted the corresponding Adeno-associated virus (AAV) intraarticular injections. Next, experimental data including immunohistochemical staining,HE/Safranin-O fast green staining,histological evidence analysis,relevant Osteoarthritis Research Society International (OARSI) scoresand expressions of molecules in cartilage anabolismindicated that the relationship betweenERK2 and USP15 throughTGF-β signaling pathway in vivo.Finally, we observed the specific mechanismof USP15 on ERK2 throughco-immunoprecipitation,deubiquitination assay, immunofluorescence and nuclear plasma separation.Results.Here, we detected that ERK2 of non-SMAD signaling can maintain the cartilage phenotype by activating the TGF-β/Smad signaling pathway throughincreasing USP15 in vitro and in vivo. Most importantly, USP15 is required during this process and can form a complex with ERK2 to regulate ubiquitination of ERK2.Specifically,USP15, instead of USP15 C269S, deubiquitinates and activates ERK2, followed by translocation of phosphorylated ERK2 from the cytoplasm to the nucleus. Correspondingly, the level of phosphorylated ERK2 was increased by injecting AAV-mediated overexpressing USP15 into the rat OA model. Conclusion.Taken together, our study revealed a positive feedback regulation between USP15 and ERK2, which plays a critical role in the interaction of SMAD and non-SMAD signaling pathways to promote cartilage repair in experimental OA.

show abstract

Weight-bearing asymmetry and vertical activity differences in a rat model of post-traumatic knee osteoarthritis

Cited by 29 publications

References 42 publications

Use of pre‐clinical surgically induced models to understand biomechanical and biological consequences of PTOA development

Use of pre‐clinical surgically induced models to understand biomechanical and biological consequences of PTOA development

Sivelestat sodium hydrate improves post-traumatic knee osteoarthritis through nuclear factor-κB in a rat model

Positive Feedback Regulation Between USP15 and ERK2 Promotes Cartilage Repair in Experimental Osteoarthritis

Contact Info

Product

Resources

About