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underlying bone tumors. Bone tumor animal models serve as the acute pathological processes differ substantially from
indispensable tools for investigating tumorigenic mechanisms, the gradual progression of human OA.
screening potential therapeutics, and evaluating treatment
efficacy. These models can be broadly categorized into three 2.2.2. Rheumatoid arthritis (RA) animal models
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principal types based on their methodological approaches: RA is a chronic systemic autoimmune disorder with an
spontaneous models, transplantation models, and genetically incompletely understood pathogenesis. Various methods,
engineered models, each offering distinct advantages for including immune dysregulation, genetic predisposition,
specific research applications. and environmental triggers, have been applied to induce
The spontaneous model employs local administration RA in animals, which have been proven to be effective
of Aflatoxin B1 or radioactive substances to recapitulate approaches for RA research. Induced arthritis models
environmentally induced carcinogenesis, and most remain the most widely utilized models. The collagen-
commonly involves dogs, which is similar to humans at induced arthritis model faithfully reproduces characteristic
the histopathological and genetic level. 61-63 At present, the synovial hyperplasia and bone erosion observed in
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spontaneous osteosarcoma (OS) model is rarely used because human RA. Spontaneous genetic models have emerged
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of the prolonged period needed and the heterogeneity of as powerful tools for studying RA pathogenesis.
Interleukin (IL)-1 receptor antagonist knockout mice
the tumor, transplantation models represent the most develop spontaneous arthritis resembling human disease.
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widely utilized methodology, which involve implanting Tumor necrosis factor-α transgenic mice exhibit chronic
cancer cells or tumoral tissue fragments directly into mice progressive polyarthritis, while SKG mice (carrying a zeta-
or rats, which can recapitulate key aspects of primary chain-associated protein kinase 70 mutation) demonstrate
bone cancer. Patient-derived xenograft models maintain β-glucan-sensitive autoimmune arthritis. 75,76
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the histopathological and molecular characteristics of
primary tumors, making them particularly suitable for 2.3. Skeletal muscle injury animal models
personalized therapy development. Genetically modified
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animal models serve as valuable tools for elucidating the Skeletal muscle injuries occur from traumatic incidents,
molecular pathways involved in bone sarcoma pathogenesis including car accidents, surgical resections, and injuries
and enable preclinical evaluation of novel therapeutic sustained on the battlefield, leading to functional loss of
approaches. In the context of OS, conditional activation of the injured muscle. Muscle injury experimental models
oncogenes or deletion of several suppressor genes known are primarily selected based on distinct pathogenic factors
to be implicated in tumor initiation and progression is a and research objectives. Mechanical injury models,
common method applied to construct transgenic mouse including volumetric muscle loss, contusion, and stretch
models. 64 models, simulate trauma in rodents, providing insights
into muscle repair. 77,78 However, standardization of injury
2.2. Cartilage-related animal models severity remains challenging. Chemical injury models,
such as cardiotoxin or barium chloride injections, enable
2.2.1. OA animal models
controlled muscle fiber damage but carry systemic risks. 79,80
OA, a chronic condition characterized by pain and Genetic engineering models, including muscle-specific gene
significant discomfort, is one of the most prevalent forms knockout constructs (e.g., MyoD / ) and muscular dystrophy
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of arthritis. Contemporary modeling approaches target models, serve as indispensable tools for elucidating genetic
distinct etiological factors, including mechanical injury, myopathies and gene-specific functions. Future research
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metabolic dysregulation, aging processes, and genetic should better mimic human muscle pathology and
predisposition. Mechanically induced OA models represent implement standardized assessment protocols to improve
the most widely utilized approach for studying abnormal clinical translatability, advancing preclinical MSK research.
stress-induced joint degeneration, including anterior
cruciate ligament transection and meniscectomy. The 2.4. Tendon and ligament injury animal models
models replicate post-traumatic secondary OA pathology Animal models of tendon and ligament injury are
and provide insights into it. 12,65,66 Metabolic OA models essential for investigating connective tissue repair
employ high-fat diets to induce obesity and metabolic mechanisms. Acute trauma models, including complete/
dysfunction, facilitating investigation of metabolic partial transection, enable precise investigation of early
syndrome-associated OA. 67-69 These models are particularly healing response, recapitulating clinical pathology with
relevant for elucidating the obesity-OA relationship in inflammatory infiltration and collagen disorganization.
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contemporary populations with increasing metabolic Chronic degeneration models utilize mechanical
disorders. Chemically induced models (e.g., sodium overloading or enzymatic induction to simulate
monoiodoacetate or collagenase injections) produce rapid tendinopathy, including glycosaminoglycan (GAG)
chondrocyte death and matrix degradation. 70,71 However, accumulation and neovascularization. Surgical repair
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Volume 1 Issue 3 (2025) 4 doi: 10.36922/OR025280024