A clinically realistic large animal model of intra-articular fracture that progresses to post-traumatic osteoarthritis

Goetz, Jessica E.; Fredericks, Douglas C.; Petersen, Emily; Rudert, Maximilian; Baer, Thomas; Swanson, Eric; Roberts, Nathan; Martin, James A.; Tochigi, Yuki

doi:10.1016/j.joca.2015.05.022

Cited by 36 publications

(58 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2A, scored in B) and concentrated on the talus (Fig. 2C, scored in D) after reproducible distal tibial fracture, as previously described (25). These were prevented at 6 months with amobarbital (n = 5 with the exception of the tibial histology where n = 4) or 10 mM NAC (n = 6).…”

Section: Resultsmentioning

confidence: 88%

“…To capture the breadth of this effect, we have used well-described, custom automated scoring algorithms (24, 25, 44–46) to provide large scale quantitation of histological changes associated with PTOA spanning the synovium, the weight-bearing areas of both articular surfaces, and the subchondral bone. Intra-articular administration of NAC or amobarbital significantly abrogated PTOA after an IAF as shown by classic PTOA indicators including PG content, cartilage thickness, and structural damage scores as well as intracellular phenomena linked to PTOA such as oxidative stress (4, 10, 11, 15, 19, 47, 48) and altered mitochondrial metabolism (10, 11, 13, 14, 17–19, 24, 27, 49).…”

Section: Discussionmentioning

confidence: 99%

“…Power analyses determined that an n = 5 was necessary to provide a greater than 80% chance to detect improvement in automated Mankin scoring based on our previous characterization of the model and associated PTOA (25). Given the expense and duration of these experiments, we decided to combine the NAC and NAC with extended release treatment groups after the first three animals in each group were analyzed because no significant difference was observed between these two NAC treatments.…”

Section: Methodsmentioning

confidence: 99%

“…Seventy five skeletally mature, 2 year old Yucatan minipigs of both genders were used. The porcine model (25) uses a severe impact to the bottom (caudal aspect) of the anesthetized animal’s foot to fracture the distal tibia, followed by surgical ORIF of the fracture. A carefully oriented stress rising saw cut through the anterior tibial cortex ensures a controlled, reproducible IAF when an impaction pendulum drives the talus into the tibia with 40 J [schematic shown in (25)].…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis

et al. 2018

View full text Add to dashboard Cite

We tested whether inhibiting mechanically-responsive articular chondrocyte mitochondria after severe traumatic injury and preventing oxidative damage represent a viable paradigm for posttraumatic osteoarthritis (PTOA) prevention. We used a porcine hock intra-articular fracture (IAF) model well suited to human-like surgical techniques and with excellent anatomic similarities to human ankles. After IAF, amobarbital or N-acetylcysteine (NAC) was injected to inhibit chondrocyte electron transport or downstream oxidative stress, respectively. Effects were confirmed via spectrophotometric enzyme assays or glutathione/glutathione disulfide assays and immunohistochemical measures of oxidative stress. Amobarbital or NAC delivered after IAF provided substantial protection against PTOA at 6 months, including maintenance of proteoglycan content, decreased histological disease scores, and normalized chondrocyte metabolic function. These data support the therapeutic potential of targeting chondrocyte metabolism after injury and suggest a strong role for mitochondria in mediating PTOA.

show abstract

Section: Resultsmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Goetz et al 32 used Yucatan miniature pigs to simulate the pathogenic course of PTOA using a special tripod fixation, using immobilization after a tibial osteotomy of 1e2 mm of the pig knee (Fig. 6).…”

Section: Intra-articular Fracture (Iaf) Model (3/34)mentioning

confidence: 99%

How to establish an expected animal model of post-traumatic osteoarthritis?

Han¹,

Chen²,

Tian³

et al. 2017

Chinese Nursing Research

View full text Add to dashboard Cite

a b s t r a c tBackground: Animal models of osteoarthritis (OA), including post-traumatic osteoarthritis and spontaneous osteoarthritis, have been established in many ways. In recent years, there have been many reports in various foreign academic journals, but animal models of post-traumatic osteoarthritis (distinct from spontaneous osteoarthritis) have rarely been established or summarized in these reports. Animal models of post-traumatic osteoarthritis show different characteristics depending on the animal species and modeling methods used, which is why we have written this article. Objective: To summarize the research progress and research status of animal models of post-traumatic osteoarthritis. Methods: A retrospective review of the animal model of post-traumatic osteoarthritis (OA) was conducted on the basis of reports retrieved from the PubMed database with the keywords for searching "animal model, post-traumatic osteoarthritis (PTOA)" from October 2006 to October 2016 and confided English language. A total of 80 academic articles on the study of animal models of traumatic osteoarthritis were retrieved, and 34 of them were included in this literature review after reading the free fulltext of them. Results: Different PTOA models based on different modeling methods and different animal species had their own characteristics. Different modeling methods should be selected according to different modeling animals. Conclusions: Considering the project funds, experimental objectives and technical conditions, appropriate experimental animal and modeling method should be selected based on synthetic considerations to obtain an appropriate PTOA model and ideal experimental results.

show abstract

N2‐Polarized Neutrophils Guide Bone Mesenchymal Stem Cell Recruitment and Initiate Bone Regeneration: A Missing Piece of the Bone Regeneration Puzzle

Cai

Lin

et al. 2021

Advanced Science

View full text Add to dashboard Cite

The role of neutrophils in bone regeneration remains elusive. In this study, it is shown that intramuscular implantation of interleukin-8 (IL-8) (commonly recognized as a chemotactic cytokine for neutrophils) at different levels lead to outcomes resembling those of fracture hematoma at various stages. Ectopic endochondral ossification is induced by certain levels of IL-8, during which neutrophils are recruited to the implanted site and are N2-polarized, which then secrete stromal cell-derived factor-1 (SDF-1 ) for bone mesenchymal stem cell (BMSC) chemotaxis via the SDF-1/CXCR4 (C-X-C motif chemokine receptor 4) axis and its downstream phosphatidylinositol 3'-kinase (PI3K)/Akt pathway and -catenin-mediated migration. Neutrophils are pivotal for recruiting and orchestrating innate and adaptive immunocytes, as well as BMSCs at the initial stage of bone healing and regeneration. The results in this study delineate the mechanism of neutrophil-initiated bone regeneration and interaction between neutrophils and BMSCs, and innate and adaptive immunities. This work lays the foundation for research in the fields of bone regenerative therapy and biomaterial development, and might inspire further research into novel therapeutic options.

show abstract

A clinically realistic large animal model of intra-articular fracture that progresses to post-traumatic osteoarthritis

Abstract: This model replicated key features of a human IAF, including surgical stabilization, inflammatory responses, and progression to osteoarthritic cartilage degeneration, thereby providing a potentially useful model for translating promising treatment options to clinical practice.

Cited by 36 publications

References 34 publications

Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis

Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis

How to establish an expected animal model of post-traumatic osteoarthritis?

N2‐Polarized Neutrophils Guide Bone Mesenchymal Stem Cell Recruitment and Initiate Bone Regeneration: A Missing Piece of the Bone Regeneration Puzzle

Contact Info

Product

Resources

About