Overexpression of secretory leukocyte peptidase inhibitor (SLPI) does not modulate experimental osteoarthritis but may be a biomarker for the disease.
Osteoarthritis Cartilage
; 29(4): 558-567, 2021 04.
Article
en En
| MEDLINE
| ID: mdl-33485930
ABSTRACT
OBJECTIVE:
Osteoarthritic cartilage destruction can be regulated by the balance between proteases and anti-proteases. Here, we sought to identify novel cellular protease inhibitors associated with osteoarthritis (OA) pathogenesis.METHODS:
Candidate molecules were screened from microarray data of chondrocytes treated with OA-associated catabolic factors. The functions of candidate molecules in OA pathogenesis were examined in primary-culture mouse articular chondrocytes and mouse models of OA, such as those stimulated by destabilization of the medial meniscus (DMM) or intra-articular (IA) injection of adenovirus expressing the candidate gene. The value of the selected candidate molecule as a biomarker of OA was examined by measuring its circulating levels in human and mouse blood.RESULTS:
Bioinformatic analysis identified secretory leukocyte peptidase inhibitor (SLPI) as a highly upregulated cellular protease inhibitor in chondrocytes treated with pathogenic catabolic factors, including interleukin (IL)-1ß, hypoxia-inducible factor (HIF)-2α, and zinc importer ZIP8. The adenovirus-mediated overexpression of SLPI in joint tissues did not cause any OA-like change or modulate DMM- or HIF-2α-induced experimental OA in mice. SLPI also did not markedly modulate the expression of OA-associated catabolic or anabolic factors in chondrocytes. However, SLPI was specifically upregulated in OA cartilage, and the serum SLPI levels were significantly elevated in human OA patients and experimental OA mice, suggesting that SLPI may be a biomarker of OA.CONCLUSION:
Although SLPI is upregulated in OA chondrocytes, it does not appear to per se modulate OA development in mice. However, it may be a potential biomarker of OA in humans and animal models.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Artritis Experimental
/
Condrocitos
/
Osteoartritis de la Rodilla
/
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
/
Inhibidor Secretorio de Peptidasas Leucocitarias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Osteoarthritis Cartilage
Asunto de la revista:
ORTOPEDIA
/
REUMATOLOGIA
Año:
2021
Tipo del documento:
Article