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Therapeutic effect of targeting Substance P on the progression of osteoarthritis
Yoshiko Shirakawa1, Tomoyuki Nakasa1,2, Munekazu Kanemitsu1
1Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Objectives:
Substance P (SP) modulates NK1 and has various functions such as regulation of pain response, bone metabolism, and angiogenesis, which are recognized as important factors in osteoarthritis (OA). We aimed to evaluate the therapeutic effect of targeting SP on OA progression.
Methods:
SP expression patterns were analysed histologically in articular cartilage and subchondral bone of human knees from OA patients and autopsy donors as non-OA samples and in mouse articular cartilage. Moreover, to examine the effect of SP on the progression of OA, we administered drugs to mice following the surgical destabilization of the medial meniscus: Phosphate-buffered saline (PBS), septide (NK1 receptor agonist), or aprepitant (NK1 receptor antagonist). Histological analysis and bone morphologic analysis using micro-computed tomography were performed.
Results:
In human analysis, the expression of SP in mild OA samples was significantly higher than that in severe OA, and that in healthy cartilage was significantly higher than that in OA. In mouse analysis, Osteoarthritis Research Society International scores in the septide group were significantly lower than those in the control group. Computed tomography analysis showed that the subchondral bone's epiphysis in the control group had sclerotic change, not observed in the septide group.
Conclusions:
The administration of septide ameliorates OA progression through preventing subchondral bone sclerosis.
Insights
Targeting Substance P (SP) with septide, an NK1 receptor agonist, may ameliorate osteoarthritis (OA) progression by preventing subchondral bone sclerosis, offering a potential therapeutic strategy for OA.
Area of Science:
- Biomedical research
- Orthopedics
- Pharmacology
Background:
- Substance P (SP) plays a role in pain, bone metabolism, and angiogenesis, key factors in osteoarthritis (OA) pathogenesis.
- NK1 receptors are modulated by SP and are implicated in OA progression.
Purpose of the Study:
- To investigate the therapeutic potential of targeting Substance P (SP) for osteoarthritis (OA) progression.
Main Methods:
- Analyzed SP expression in human OA and non-OA cartilage and subchondral bone.
- Administered PBS, septide (NK1 agonist), or aprepitant (NK1 antagonist) to mice with surgically induced OA.
- Performed histological and micro-computed tomography analyses to assess OA progression and subchondral bone changes.
Main Results:
- Human SP expression was higher in mild OA than severe OA, and higher in healthy cartilage than OA.
- Septide treatment in mice significantly reduced Osteoarthritis Research Society International scores compared to controls.
- Micro-CT revealed reduced subchondral bone sclerosis in the septide-treated group compared to controls.
Conclusions:
- Septide administration ameliorates OA progression.
- Targeting SP via NK1 receptor agonism prevents subchondral bone sclerosis in OA.
