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Animal models remain indispensable in MSK system models of the MSK system, aiming to offer valuable insights
disease research due to their unique ability to replicate and references for researchers in this field.
human pathophysiology, providing invaluable insight into
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medical knowledge and alleviation of human suffering. 2. Animal models of the MSK system
Through precise model establishment, including surgically In MSK system biomedical research, skeletal animal models
induced OA or genetically modified muscular dystrophy are indispensable tools for investigating disease pathogenesis,
models, researchers have successfully replicated the complex evaluating therapeutic interventions, and developing
physiological environment of the human MSK system. 12,13 regenerative strategies. These experimental models replicate
With the advanced technologies, animal models not only critical pathological features of human skeletal disorders,
facilitate longitudinal monitoring of disease progression including OP, fracture nonunion, and bone neoplasms,
but also enable comprehensive functional assessment through various construction methods, such as surgical
through motor behavior analysis. This allows researchers to intervention, pharmacological induction, genetic engineering,
systematically investigate disease mechanisms and progression. or age-related modeling. The establishment of reliable animal
In therapeutic development, animal studies serve as a critical models provides an essential foundation for advancing the
platform for validating novel biomaterials, pharmacological treatment of MSK diseases and helps to translate basic research
agents, and surgical interventions. 14-18 The pharmacokinetic, results into clinical applications (Figure 1).
biocompatibility, and safety data derived from these preclinical
studies are fundamental for clinical translation. Up to now, 2.1. Bone-related animal models
notable successes have been achieved in animal models, which 2.1.1. OP animal models
include neural regeneration strategies developed through
spinal cord injury (SCI) models and prosthetic joint designs OP is a systemic metabolic bone disorder and a major global
optimized through large-animal biomechanical testing. 19,20 public health concern, imposing substantial burdens on
healthcare systems, particularly in aging populations. 27-29
Organoids, three-dimensional (3D) structures derived Animal models of OP are essential for studying bone
from stem cells or tissue-specific progenitors, are miniature metabolism disorders and evaluating therapeutic strategies.
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and simplified in vitro model systems that mimic the structure The ovariectomy (OVX) model remains the gold standard for
and function of organs. 21-23 These miniature organ analogs postmenopausal OP research, demonstrating characteristic
replicate key functional and structural characteristics of trabecular thinning and reduced bone mineral density
native tissues, including myofiber contraction, bone matrix that mirror clinical manifestations. 30-33 Glucocorticoid-
mineralization, and cartilage mechanical properties. 24,25 induced OP, established through chronic administration of
Compared to animal models, organoid systems offer prednisolone or similar agents, replicate iatrogenic OP and
distinct advantages, including high-throughput screening are valuable for assessing anabolic treatment. 30,34 Disuse OP
capacity, precise experimental control, and reduced ethical models employ tail suspension or surgical immobilization to
concerns. 21,26 These features make organoids particularly study mechanical unloading effects, enabling investigation of
valuable for preliminary mechanistic studies, drug toxicity mechanotransduction pathways and physical rehabilitation
assessments, and genetic manipulation experiments. interventions. 35,36 Age-related OP models utilize senescent
However, current organoid technologies face significant rodents (typically 18–24 months old) to investigate low bone
limitations, most notably the lack of vascular networks, turnover and progressive bone loss. 37-39 Genetic modification
neural innervation, hormone regulation, mechanical OP models involve manipulation of key regulatory
stimulation, and immune components, all of which are genes (e.g., receptor activator of nuclear factor-κB ligand
essential to MSK physiology and pathology. [RANKL], osteoclastogenesis inhibitory factor [OPG], and
Despite the emergence of innovative technologies, such sclerostin) and elucidate specific genetic contributions to
as organoids, comprehensive evaluation of MSK-related bone homeostasis and disease progression. 40,41 These models
diseases still relies on animal models, particularly for collectively advance understanding of OP pathogenesis and
assessing systemic functional recovery, a capability beyond therapeutic development.
current in vitro systems. This review systematically explores
the complementary roles of MSK system organoids and 2.1.2. Fracture animal models
animal models, highlighting the potential for organoid Animal fracture models serve as essential tools for
technology to reduce reliance on animal experimentation. investigating bone regeneration mechanisms, evaluating
It also critically evaluates the current limitations of MSK therapeutic interventions, and examining disease-related
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organoids and outlines future directions for improving influences on fracture healing. Current modeling
organoid construction and functionality. Overall, the approaches primarily focus on distinct clinical fracture
review provides an overview of recent advances and etiologies, including traumatic fractures, osteoporotic
applications in both MSK system organoids and animal fractures, infectious fractures, and non-union conditions. 43

Volume 1 Issue 3 (2025) 2 doi: 10.36922/OR025280024