Morphological and neuromuscular junction signaling pathways changes in rats with knee osteoarthritis induced by anterior cruciate ligament transection

• Grant number: 16/24666-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2017
• End date: February 28, 2018
• Field of knowledge: Health Sciences - Physiotherapy and Occupational Therapy
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Tania de Fatima Salvini
• Grantee: Jonathan Emanuel da Cunha
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Osteoarthritis is a degenerative disease involving joints and periarticular tissues in which the knee is the most affected joint. Knee osteoarthritis (KOA) is characterized by inflammatory mediators increase, joint-space narrowing, osteophytes formation, pain and swelling. KOA promotes weakness and muscle atrophy that accelerate the destruction of cartilage and modify functional movement. However, there is no scientific evidence on neuromuscular signaling pathways related to changes in KOA. The study hypothesis is that the functional and muscular impairments in KOA are associated with changes in the neuromuscular junction. Aim: To evaluate the neuromuscular junction morphology, cross-sectional area of muscle fibers, the expression of genes linked to muscle atrophy (atrogin-1 and Murf-1) and the neuromuscular junction (nAChR, Agrin, Musk, Rapsyn) of the quadriceps, gastrocnemius, and tibialis anterior in rats with unilateral KOA induced by anterior cruciate ligament transection (ACLT). Methods: Adult male rats (Wistars) will be randomly allocated into 2 groups (n=20/group): control - no intervention; KOA - ACLT knee surgery. After 60 days, the animals will be evaluated regarding: pain (Von Frey), swelling (electronic calipers), gait (gait analysis), synovial fluid of the knee joint (dosage of inflammatory markers), joint morphology (Mankin score) muscle (cross-sectional area, gene expression, morphology end plate and protein analysis). The results will be analysed as their normality and homogeneity distributions. The statistical difference between groups will be assessed by using student t test or Mann-Whitney. In conclusion, the findings of this study may provide new scientific evidence about the changes at the neuromuscular signaling pathways in KOA. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BARBOSA, GERMANNA MEDEIROS; CUNHA, JONATHAN EMANUEL; CUNHA, THIAGO MATTAR; MARTINHO, LIZANDRA BOTARO; TOME SOUZA CASTRO, PAULA AIELLO; BEZERRA OLIVEIRA, FRANCISCO FABIO; CUNHA, FERNANDO QUEIROZ; RAMALHO, FERNANDO SILVA; SALVINI, TANIA FATIMA. Clinical-like cryotherapy improves footprint patterns and reduces synovial inflammation in a rat model of post-traumatic knee osteoarthritis. SCIENTIFIC REPORTS, v. 9, OCT 10 2019. (15/26567-2, 16/24666-6)

CUNHA, JONATHAN EMANUEL; BARBOSA, GERMANNA MEDEIROS; TOME DE SOUZA CASTRO, PAULA AIELLO; FERREIRA LUIZ, BEATRIZ LEITE; ARCARI SILVA, ANDREZA CRISTINE; RUSSO, THIAGO LUIZ; VASILCEAC, FERNANDO AUGUSTO; CUNHA, THIAGO MATTAR; CUNHA, FERNANDO QUEIROZ; SALVINI, TANIA FATIMA. Knee osteoarthritis induces atrophy and neuromuscular junction remodeling in the quadriceps and tibialis anterior muscles of rats. SCIENTIFIC REPORTS, v. 9, APR 24 2019. (15/26567-2, 16/24666-6)

BARBOSA, GERMANNA M.; CUNHA, JONATHAN E.; RUSSO, THIAGO L.; CUNHA, THIAGO M.; CASTRO, PAULA A. T. S.; OLIVEIRA, FRANCISCO F. B.; CUNHA, FERNANDO Q.; RAMALHO, FERNANDO S.; SALVINI, TANIA F.. Thirty days after anterior cruciate ligament transection is sufficient to induce signs of knee osteoarthritis in rats: pain, functional impairment, and synovial inflammation. Inflammation Research, v. 69, n. 3, p. 279-288, MAR 2020. (15/26567-2, 16/24666-6)