Musculoskeletal Diseases
Maintaining proper physiological functions within a cell requires a balanced level of iron, the disruption of which is recognized as a potential contributing factor to a number of musculoskeletal disorders. Protheragen is focused on promoting research in musculoskeletal disorders, which includes a wide range of conditions that involve the pathologies of bone, joint, muscle, ligament, or tendon. Our focus is on the various aspects of iron metabolism in relation to musculoskeletal disorders, providing comprehensive services from biological target identification to the therapy development stages, including preclinical trials.
Overview of Musculoskeletal Diseases
Disabilities caused by chronic musculoskeletal disorders like osteoarthritis, osteoporosis, intervertebral disc degeneration, sarcopenia, rheumatoid arthritis, and rhabdomyolysis are on the rise, along with their burden on healthcare systems globally. Although many individual factors are known to influence the progression of such disorders, the role of iron homeostasis is proving to be of paramount importance.
Fig.1 Muscular iron metabolism and ferroptosis. (Ru, Q., et al., 2025)
Iron Metabolism Abnormalities in Musculoskeletal Diseases
Iron is important for the proper functioning of cells within organ systems of mammals; particularly, iron balance is important for the health of joints. Improperly managed iron metabolism can be very harmful, leading to oxidative stress, inflammation, and damage to tissues and cells. In regard to musculoskeletal disorders, both overload and deficient iron within the body have been shown to have an effect.
- Iron Overload
Diseases such as hereditary hemochromatosis may accumulate excess iron in certain organs, such as joints, which may further intensify inflammation and damage in arthritis. Overloaded iron worsens bone disease by ferroptosis to suppressing osteoblast function and differentiation, contributing to the increasingly appreciated pathobiology of many musculoskeletal disorders.
- Iron Deficiency
Iron deficiency has the potential to impair collagen synthesis as well as bone formation, which may predispose individuals to conditions such as osteoporosis and decreased bone mineral density. In iron deficiency, both osteoclast and osteoblast activity are affected due to the absence of iron in sufficient quantities to power the processes of bone resorption and formation of energy, respectively.
Fig.2 Possible role of excess iron in arthropathy development. (Sun, K., et al., 2021)
The connection between iron metabolism and musculoskeletal disorders is intricate, including several important pathologic mechanisms.
Elevated reactive oxygen species (ROS), which are the outcome of iron imbalance and the Fenton reaction, lead to oxidative stress, which initiates inflammation, triggering further destruction of the joints and soft tissue.
Another important mechanism is ferroptosis, which is an iron-dependent form of lipid peroxidation. Dysregulation of ferroptosis is noted in osteoarthritis, sarcopenia, and other musculoskeletal disorders.
Dysregulation of iron can directly alter the activity of bone cells. Increased levels of iron can enhance the construction of osteoclasts and suppress the formation of osteoblasts, thus promoting bone destruction in osteoporosis.
Therapeutics Development for Musculoskeletal Diseases
| Diseases | Drug Name | Mechanism of Action | Targets | Research Phase |
| Osteoarthritis | Deferoxamine | Inhibit NCOA4 expression and restore ferritin level, and chelate excessive iron. | Iron overload | Preclinical |
| Restless Legs Syndrome | Ferric carboxymaltose | Restoration of iron in the brain, which supports the healthy functioning of the dopaminergic system. | Iron supplementation | Phase II/III |
| Sarcopenia | Deferiprone | Reduces excessive or dysregulated iron accumulation, thereby potentially mitigating muscle loss and dysfunction. | Iron overload | Preclinical |
| Osteoporosis | sh-Repin1 | The knockdown of Repin1 reduces the expression of Lcn2 and reduces the harmful impact of excess iron within cells. | Repin1 | Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a therapy plan recommendation. For guidance on therapy options, please visit a regular hospital.
Our Services
At Protheragen, we apply our knowledge in iron metabolism to provide a complete list of drug development services for musculoskeletal disorders, expediting your research starting from the discovery stage all the way to preclinical evaluation. We provide a suite of services that includes the development of diagnostics, therapeutics, and disease models, alongside preclinical research, which encompasses pharmacokinetic and biosafety studies.
Types of Musculoskeletal Diseases
- Ankylosing Spondylitis
- Duchenne Muscular Dystrophy
- Gout arthritis
- Hemophilic Arthropathy
- Osteoarthritis
- Osteoporosis
- Restless Legs Syndrome
- Sarcopenia
Animal Model Development Services for Musculoskeletal Diseases
To study the intricate relationships linking iron metabolism with musculoskeletal disorders, as well as to evaluate new therapeutics by investigating their efficacy and safety, animal models are crucial. For musculoskeletal disease research, we offer various established and customizable animal models.
| Animal Models | Diseases | Types |
| Ferric ammonium citrate (FAC)-induced model | Osteoporosis | Chemical-induced model |
| Ovariectomy (OVX)-induced model | Osteoporosis | Surgical animal model |
| Monosodium iodoacetate (MIA)-induced model | Osteoarthritis | Chemical-induced model |
| Iron-deficient diet-induced model | Restless Legs Syndrome | Diet-induced model |
| Disuse model | Sarcopenia | Induced animal model |
| SAMP8 mouse model | Sarcopenia | Spontaneous model |
Pharmacokinetics and Drug Safety Evaluation Services
Work with Protheragen and leverage our unique and one-stop services related to iron metabolism to advance your research and development projects in musculoskeletal diseases. For any inquiries regarding our services, reach out to us.
References
- Ru, Qin et al. "Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects." Bone research 13.1 (2025): 27.
- Sun, Kai et al. "Iron homeostasis in arthropathies: From pathogenesis to therapeutic potential." Ageing research reviews 72 (2021): 101481.