Early Changes of Articular Cartilage and Subchondral Bone in The DMM Mouse Model of Osteoarthritis

Fang, Hang; Huang, Lisi; Welch, Ian; Norley, Chris J. D.; Holdsworth, David W.; Beier, Frank; Cai, Daozhang

doi:10.1038/s41598-018-21184-5

Cited by 156 publications

(161 citation statements)

References 25 publications

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“…In this method, the medial collateral ligaments are cut in order to expose the meniscus. Then, the surgeon severs the meniscus to destabilize the joint [25]. Either the lateral or medial meniscus can be chosen for transection.…”

Section: Surgically Induced Modelsmentioning

confidence: 99%

“…In mice, it is more common to sever the medial meniscus as it generally bears a heavier load and thus is more likely to lead to the development of OA when it is severed [25]. When the medial meniscus is severed, this method is often referred to as destabilization of the medial meniscus or DMM [25]. This method produces rapidly progressing PTOA with characteristics that mirror the progression of the disease in humans.…”

Section: Surgically Induced Modelsmentioning

confidence: 99%

“…This method produces rapidly progressing PTOA with characteristics that mirror the progression of the disease in humans. In humans, 50% of people who undergo a meniscectomy develop OA within 20 years of the date of the surgery [25]. In mice, mild osteoarthritic defects begin to develop rapidly after the procedure is performed.…”

Section: Surgically Induced Modelsmentioning

confidence: 99%

“…Naturally occurring X X X X [9][10][11] Genetically modified X X X X [12][13][14][15][16][17][18][19][20][21][22][23][24] Surgically induced (all) X X X X X [25][26][27][28][29][30] Chemically induced (all) X [31][32][33][34][35][36][37][38][39] Non-invasive induction X X X X X [40][41][42][43][44][45][46][47][48][49][50][51][52] [5,8,63,64]…”

Section: Referencesmentioning

confidence: 99%

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Pros and cons of mouse models for studying osteoarthritis

Bapat¹,

Hubbard²,

Munjal³

et al. 2018

Clinical & Translational Med

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Osteoarthritis (OA) is one of the most common chronic conditions in the world today. It results in breakdown of cartilage in joints and causes the patient to experience intense pain and even disability. The pathophysiology of OA is not fully understood; therefore, there is currently no cure for OA. Many researchers are investigating the pathophysiology of the disease and attempting to develop methods to alleviate the symptoms or cure the OA entirely using animal models. Most studies on OA use animal models; this is necessary as the disease develops very slowly in humans and presents differently in each patient. This makes it difficult to effectively study the progression of osteoarthritis. Animal models can be spontaneous, in which OA naturally occurs in the animal. Genetic modifications can be used to make the mice more susceptible to developing OA. Osteoarthritis can also be induced via surgery, chemical injections, or non-invasive trauma. This review aims to describe animal models of inducing osteoarthritis with a focus on the models used on mice and their advantages and disadvantages that each model presents.

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Section: Surgically Induced Modelsmentioning

confidence: 99%

Section: Surgically Induced Modelsmentioning

confidence: 99%

Section: Surgically Induced Modelsmentioning

confidence: 99%

Section: Referencesmentioning

confidence: 99%

See 2 more Smart Citations

Pros and cons of mouse models for studying osteoarthritis

Bapat¹,

Hubbard²,

Munjal³

et al. 2018

Clinical & Translational Med

View full text Add to dashboard Cite

show abstract

“…These include biological hypotheses such as cell death or vascular changes and mechanical hypotheses such as rod and plate distribution in subchondral bone (40)(41)(42). We tested the hypothesis that MMP13 ocy-/bone causes increased chondrocyte catabolism and apoptosis.…”

Section: Mechanisms Of Subchondral Osteocyte Influence On Cartilagementioning

confidence: 99%

Suppressed Osteocyte Perilacunar / Canalicular Remodeling Plays a Causal Role in Osteoarthritis

Mazur

Woo

Yee

et al. 2019

Preprint

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Osteoarthritis (OA), long considered a primary disorder of articular cartilage, is commonly associated with subchondral bone sclerosis. However, the cellular mechanisms responsible for changes to subchondral bone in OA, and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration, remain unclear. In knee joints from human patients with end-stage OA, we found evidence of profound defects in osteocyte function.Suppression of osteocyte perilacunar/canalicular remodeling (PLR) was most severe in OA subchondral bone, with lower protease expression, diminished canalicular networks, and disorganized and hypermineralized extracellular matrix. To determine if PLR suppression plays a causal role in OA, we ablated the PLR enzyme MMP13 in osteocytes, while leaving chondrocytic MMP13 intact. Not only did osteocytic MMP13 deficiency suppress PLR in cortical and subchondral bone, but it also compromised cartilage. Even in the absence of injury, this osteocyte-intrinsic PLR defect was sufficient to reduce cartilage proteoglycan content and increase the incidence of cartilage lesions, consistent with early OA. Thus, in humans and mice, osteocyte PLR is a critical regulator of cartilage homeostasis. Together, these findings implicate osteocytes in bone-cartilage crosstalk in the joint and identify the causal role of suppressed perilacunar/canalicular remodeling in osteoarthritis.Recent reports have reinvigorated interest in the active role of osteocytes in remodeling their surrounding bone matrix -a process called perilacunar/canalicular remodeling (PLR) (7-10). PLR is a dynamic process by which osteocytes secrete matrix metalloproteinases (MMPs) (11-13), cathepsin K (CatK) (8), and other enzymes (14,15) to dynamically resorb and then replace the local bone matrix. PLR maintains bone material properties (11,16,17), systemic mineral homeostasis (8,10), and the canalicular channels that facilitate osteocyte communication, mechanosensation, and nourishment (7,18,19). Several known regulators of bone homeostasis,

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Treatment with Mesenchymal Stem Cell‐Derived Nanovesicle‐Containing Gelatin Methacryloyl Hydrogels Alleviates Osteoarthritis by Modulating Chondrogenesis and Macrophage Polarization

Pang

Jin

et al. 2023

Adv Healthcare Materials

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Osteoarthritis is a degenerative disorder that can severely affect joints, and new treatment strategies are urgently needed. Administration of mesenchymal stem cell (MSC)‐derived exosomes is a promising therapeutic strategy in osteoarthritis treatment. However, the poor yield of exosomes is an obstacle to the use of this modality in the clinic. Herein, a promising strategy is developed to fabricate high‐yield exosome‐mimicking MSC‐derived nanovesicles (MSC‐NVs) with enhanced regenerative and anti‐inflammatory capabilities. MSC‐NVs are prepared using an extrusion approach and are found to increase chondrocyte and human bone marrow MSC differentiation, proliferation, and migration, in addition to inducing M2 macrophage polarization. Furthermore, gelatin methacryloyl (GelMA) hydrogels loaded with MSC‐NVs (GelMA‐NVs) are formulated, which exhibit sustained release of MSC‐NVs and are shown to be biocompatible with excellent mechanical properties. In a mouse osteoarthritis model constructed by surgical destabilization of the medial meniscus (DMM), GelMA‐NVs effectively ameliorate osteoarthritis severity, reduce the secretion of catabolic factors, and enhance matrix synthesis. Furthermore, GelMA‐NVs induce M2 macrophage polarization and inflammatory response inhibition in vivo. The findings demonstrate that GelMA‐NVs hold promise for osteoarthritis treatment through modulation of chondrogenesis and macrophage polarization.

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Early Changes of Articular Cartilage and Subchondral Bone in The DMM Mouse Model of Osteoarthritis

Cited by 156 publications

References 25 publications

Pros and cons of mouse models for studying osteoarthritis

Pros and cons of mouse models for studying osteoarthritis

Suppressed Osteocyte Perilacunar / Canalicular Remodeling Plays a Causal Role in Osteoarthritis

Treatment with Mesenchymal Stem Cell‐Derived Nanovesicle‐Containing Gelatin Methacryloyl Hydrogels Alleviates Osteoarthritis by Modulating Chondrogenesis and Macrophage Polarization

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