Transcriptome-wide gene regulation by gentle treadmill walking during the progression of monoiodoacetate-induced arthritis

Abstract

Objective. Physiotherapies are the most widely recommended conservative treatment for arthritic diseases. The present study was undertaken to examine the molecular mechanisms underlying the effects of gentle treadmill walking (GTW) on various stages of monoiodoacetate-induced arthritis (MIA) to elucidate the basis for the success or failure of such therapies in joint damage.Methods. Knees were obtained from untreated control rats, rats with MIA that did not undergo GTW, rats with MIA in which GTW regimens were started 1 day post-MIA induction, and rats with MIA in which GTW regimens were started after cartilage damage had progressed to grade 1 or grade 2. The cartilage was examined macroscopically, microscopically, and by microfocal computed tomography imaging. Transcriptome-wide gene expression analysis was performed, and microarray data were assessed by Ingenuity Pathways Analysis to identify molecular functional networks regulated by GTW.Results. GTW intervention started on day 1 post-MIA induction significantly prevented the progression of MIA, but its efficacy was reduced when implemented on knees exhibiting close to grade 1 cartilage damage.GTW accelerated cartilage damage in knees with close to grade 2 damage. Transcriptome-wide gene expression analysis revealed that GTW intervention started 1 day post-MIA inception significantly suppressed inflammation-associated genes and up-regulated matrixassociated gene networks. However, delayed GTW intervention after grade 1 damage had occurred was less effective in suppressing proinflammatory genes or upregulating matrix synthesis.Conclusion. The present findings suggest that GTW suppresses proinflammatory gene networks and up-regulates matrix synthesis to prevent progression of cartilage damage in MIA-affected knees. However, the extent of cartilage damage at the initiation of GTW may be an important determinant of the success or failure of such therapies.

Acute Ankle Sprain in a Mouse Model: Changes in Knee-Joint Space

“…In the rats that had knee OA induced, walking on a treadmill (12 m/min for 45 min/d) prevented further cartilage destruction. 37 There are some limitations in the current study. We used diagnostic ultrasound to measure knee-joint space in the mice.…”

“…The mice used in the current study are not genetically predisposed to knee OA, and thus, the injury to the ankle or the subsequent decreased physical activity (or both) may have caused the observed knee-joint degeneration. In another study 37 of rats, gentle treadmill walking suppressed proinflammatory gene networks and upregulated matrix synthesis to prevent progression of cartilage damage in induced arthritis. In the rats that had knee OA induced, walking on a treadmill (12 m/min for 45 min/d) prevented further cartilage destruction.…”

Mechanosignaling in Bone Health, Trauma and Inflammation

“…Both in vivo and in vitro systems have been used to study mechanotransduction; in vitro studies have utilized primary cultures of osteocytes, osteoblasts, osteoblast-like cells, and osteoclasts in monolayers and 3D scaffolds, while in vivo studies employ experimental animal models (22,66,68,122). It is as yet unclear how mechanosignals perceived by the candidate sensors b-integrin/FAK complexes trigger a vast variety of signaling cascades.…”

“…These observations have prompted investigations to examine the anti-inflammatory effects of mechanical loading in experimental models of knee osteoarthritis (32,66). According to these investigations, exercise effectively suppresses inflammation of cartilage and bone.…”

“…The inhibition of bone loss by exercise corresponds with inhibition of NOS2 and TNF-a mRNA expression in the trabecular bone in comparison to bones showing successive progression of MIA. The inhibition of the progression of MIA in response to exercise demonstrates the potential of mechanosignaling in preferentially targeting the NF-jB signaling cascade to suppress catabolic activities in inflamed tissue (65,66).…”