Angiotensin II triggers knee joint lesions in experimental osteoarthritis

de Sá, Grazielle A.; dos Santos, Anna Clara P. M.; Nogueira, Júlia M.; dos Santos, Diogo M.; Amaral, Flávio A.; Jorge, Erika C.; Caliari, Marcelo V.; Queiroz-Junior, Celso M.; Ferreira, Anderson J.

Affiliations

¹Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

²Department of Metallurgical Engineering and Materials, Institute of Exact Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

³Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

⁴Department of General Pathology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

Abstract and keywords

Objectives: This study aimed to evaluate the involvement of Angiotensin II (Ang II) in joint lesions associated with osteoarthritis (OA) in vitro and in vivo.

Methods: Chondrocyte cultures were obtained from knee joints of neonatal rats and stimulated with Ang II/MIA/ACE inhibitors. In vivo, rats treated or not with the ACE inhibitor captopril, received daily injections of Ang II or sodium monoiodoacetate (MIA) in knee joints for evaluation of cartilage, bone, and synovial lesions.

Results: Cultured chondrocytes expressed the mRNA for Ace, Agtr1, Agtr2, and Mas1. Stimulating cells with Ang II reduced chondrocyte viability and metabolism. Accordingly, in vivo Ang II injection into the knees of rats triggered hyperalgesia, joint edema, increased the number of leukocytes in the joint cavity, and induced cartilage lesions associated with OA alterations. In further experiments, Ang II synthesis was prevented with the ACE inhibitor Captopril in the context of MIA-induced OA. Ang II inhibition with captopril improved the OARSI score, induced chondroprotection, and reduced the leukocyte recruitment from synovium after MIA. Additionally, captopril prevented MIA-induced bone resorption, by decreasing the number of osteoclasts and increasing the expression of IL-10 in the bone. In vitro, inhibiting Ang II synthesis decreased MIA-induced chondrocyte death and increased Col2a1 transcription.

Conclusion: Ang II induces chondrocyte death and joint tissue damages associated with OA and its modulation can be a therapeutic strategy in osteoarthritis.

Keywords: Angiotensin II; Captopril; Knee; Chondroprotection; Bone fibrous tissue; Sodium monoiodoacetate

Links

DOI: 10.1016/j.bone.2021.115842

PubMed: 33422700

WoS: 000623118400007

History

Received: 2020-08-19

Revised: 2021-01-4

Accepted: 2021-01-4

Online: 2021-01-7

Cited Works (3)

Year	Entry
2001	Pelletier J-P, Martel-Pelletier J, Abramson SB. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum. June 2001;44(6):1237-1247.
2011	Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet. June 18, 2011;377(9783):2115-2126.
2006	Pritzker KPH, Gay S, Jimenez SA, Ostergaard K, Pelletier J-P, Revell PA, Salter D, van den Berg WB. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage. January 2006;14(1):13-29.