Muscle wasting in osteoarthritis model induced by anterior cruciate ligament transection

Abstract

This study aimed to investigate the molecular pathways involved in muscle wasting in an animal model of osteoarthritis (OA) induced by anterior cruciate ligament transection (ACLT) in rats. Reduction of protein syntheses, increased proteolysis and impaired muscle regeneration are important pathways related to muscle wasting, and myogenin, MyoD, myostatin and MuRF-1 are some of their markers. Female Wistar rats were allocated into two groups: OA (submitted to the ACLT) and SHAM (submitted to surgery without ACLT). Nociception, spontaneous exploratory locomotion and body weight of animals were evaluated weekly. Twelve weeks after the disease induction, animals were euthanized, and the right knee joints were collected. Gastrocnemius muscle of the right hind paw were dissected and weighed. Gastrocnemius was used for evaluation of muscle atrophy and expression of IL-1β, TNF-α, Pax7, myogenin, MyoD, myostatin and MuRF-1. Histopathology of the knee confirmed the development of the disease in animals of OA group. Gastrocnemius of OA animals showed a reduction of about 10% in area and an increased IL-1β expression compared to animals of SHAM group. Expression of myostatin was increased in OA group, while myogenin expression was decreased. TNF-α, Pax7, MuRF-1 and MyoD expression was similar in both OA and SHAM groups. Nociception was significantly elevated in OA animals in the last two weeks of experimental period. Spontaneous exploratory locomotion, body weight and weight of gastrocnemius showed no difference between OA and SHAM groups. Gastrocnemius atrophy in OA induced by ACLT involves elevated expression of IL-1β within the muscle, as well as increased expression of myostatin and decreased expression of myogenin. Therefore, muscle wasting may be linked to impaired muscle regeneration.

Oral shea nut oil triterpene concentrate supplement ameliorates pain and histological assessment of articular cartilage deterioration in an ACLT injured rat knee osteoarthritis model

“…Notably, the reductions in both the TG level and body weight could be indirect effects of the oral supplement. OA-induced muscle wasting is observed in both humans and rats with OA due to avoidance of physical activity under chronic OA pain [45–47]. In contrast, a proper exercise intervention not only reduced cartilage degeneration in a rat OA model but also improved physical function in a human study [48, 49].…”

Circulating Myostatin Levels Decrease Transiently after Implantation of a Hip Hemi-Arthroplasty

“…In another experimental study, 3 systemic injections of a MSTN in- hibitor within 2 weeks after musculoskeletal injury enhanced bone healing and muscle regeneration [8]. Two experimental studies [25,26] investigating muscle-wasting induced by transection of the anterior cruciate ligament and a biopsy study of patients with osteoarthritis undergoing total hip arthroplasty [11] showed increased levels of intramuscular MSTN mRNA during the first few days after surgery. However, 3 [6,11,25] of the 5 studies investigating intramuscular MSTN mRNA did not include analysis of the protein.…”

“…However, 3 [6,11,25] of the 5 studies investigating intramuscular MSTN mRNA did not include analysis of the protein. Silva et al [26] investigated protein expression and only found the MSTN propeptide (52 kDa) but not the mature MSTN peptide (26 kDa). Roh et al [24] also targeted a relatively large protein (43 kDa).…”

Skeletal Muscle Wasting and Its Relationship With Osteoarthritis: a Mini-Review of Mechanisms and Current Interventions

“…Several studies have shown that a decrease in lower limb lean mass is frequent in OA patients [ 11 ], and this is associated with a greater risk of falls [ 12 – 14 ]. Progressive muscle weakness in OA is also associated with muscle fibre atrophy, with studies demonstrating 12–19% reduction in cross-sectional area of muscles in patients with hip and knee OA [ 6 ]. Moreover, muscle damage is associated with articular cartilage degeneration [ 15 ], whereas the increased cross-sectional area of v astus medialis is associated with improved structural changes at the knee and reduced pain in OA patients [ 16 ].…”

“…On the other hand, it has been suggested that the disuse of an OA affected joint, due to the pain of movement, may be the primary cause of the reduction in muscle strength associated with OA [ 27 ]. To add to the complexity, data from a study investigating muscle wasting in an anterior cruciate ligament transection (ACLT) model of OA suggest that disuse does not fully explain the muscle wasting observed in OA patients [ 6 ]. Results of this research show that rats in the OA group display the same pattern of movement as those of SHAM group (i.e., rats submitted to surgery without ALCT).…”