Background & Aims
Osteoarthritis (OA), also known as degenerative joint disease, is a common joint disorder that results from the progressive loss of articular cartilage. This loss of cartilage can occur due to a variety of factors including wear and tear, joint injury, and genetic predisposition. Previous studies have shown the significant roles of associated skeletal muscles in the development of OA and its symptoms and function. In that study, a new Muscle Enhancement and Support Therapy (MEST) device was utilized to intramuscularly deliver biodegradable cog polydioxanone (PDO) filaments, designed to anchor and stimulate the surrounding muscle tissues within the quadriceps. The current study examined the efficacy of MEST treatment for alleviating pain in a monoiodoacetate (MIA)-induced OA animal model. Assessment of muscle injury and recovery following MEST involved analyzing biomarkers, tissue morphology, muscle mass, and strength.
Methods
Knee OA was induced in Sprague-Dawley rats via monoiodoacetate injections. MEST or sham treatment was performed in OA or Naïve rat quadriceps. Paw withdrawal threshold and weight-bearing assessed pain. Quadriceps injury and recovery via MEST were evaluated using biomarkers, tissue morphology, muscle mass, contractile force, and hindlimb torque. Satellite cell and macrophage activation, along with their activators, were also assessed. Data were compared at 1- and 3 weeks post-MEST treatment (M-W1 and M-W3).
Results
MEST treatment in OA rats caused muscle injury, indicated by elevated serum aspartate transferase and creatinine kinase levels, and local ?-actin changes at M-W1. This injury triggered pro-inflammatory macrophage and satellite cell activation, accompanied by heightened interleukin-6 and insulin-like growth factor-1 levels. However, by M-W3, these processes gradually shifted towards inflammation resolution and muscle restoration. This was seen in anti-inflammatory macrophage phenotypes, sustained satellite cell activation, and injury markers regressing to baseline. Quadriceps recovery in mass and strength from atrophy correlated with substantial OA pain reduction at M-W3.
Conclusions
Collectively, our results unveil that the MEST intervention in atrophic quadriceps muscles of OA animals induced minor muscle damage, subsequently activating both macrophages and satellite cells in concurrence with the upregulation of their activators. These changes exhibited a gradual attenuation over several weeks, ultimately contributing to muscle recovery from atrophy and relief from OA pain. Our findings provide strong support for the notion that targeting the restoration of key skeletal muscles associated with the OA joint through MEST presents a promising avenue for new OA pain treatment, although it may not be a direct remedy for OA itself. Additional research is mandatory to explore the effects of MEST on the knee joint and articular nociceptor sensitization, providing a deeper understanding of the mechanisms underlying OA pain relief. As MEST represents a novel approach, further rigorous clinical trials are also crucial to establish its safety and efficacy.
References
[1] H. Hsu, R.M. Siwiec, Knee osteoarthritis, (2018).
[2] K. Fu, S.R. Robbins, J.J. McDougall, Osteoarthritis: the genesis of pain, Rheumatology, 57 (2018) iv43-iv50.
[3] E. Shorter, A.J. Sannicandro, B. Poulet, K. Goljanek-Whysall, Skeletal Muscle Wasting and Its Relationship With Osteoarthritis: a Mini-Review of Mechanisms and Current Interventions, Curr Rheumatol Rep, 21 (2019) 40.
[4] P. Krishnasamy, M. Hall, S.R. Robbins, The role of skeletal muscle in the pathophysiology and management of knee osteoarthritis, Rheumatology (Oxford), 57 (2018) iv124.
[5] B.E. Oiestad, C.B. Juhl, A.G. Culvenor, B. Berg, J.B. Thorlund, Knee extensor muscle weakness is a risk factor for the development of knee osteoarthritis: an updated systematic review and meta-analysis including 46 819 men and women, Br J Sports Med, 56 (2022) 349-355.
[6] N.A. Segal, N.A. Glass, Is quadriceps muscle weakness a risk factor for incident or progressive knee osteoarthritis?, Phys Sportsmed, 39 (2011) 44-50.
[7] A.M. Imoto, M.S. Peccin, V.F. Trevisani, Quadriceps strengthening exercises are effective in improving pain, function and quality of life in patients with osteoarthritis of the knee, Acta Ortop Bras, 20 (2012) 174-179.
[8] B.E. Oiestad, C.B. Juhl, I. Eitzen, J.B. Thorlund, Knee extensor muscle weakness is a risk factor for development of knee osteoarthritis. A systematic review and meta-analysis, Osteoarthritis Cartilage, 23 (2015) 171-177.
Presenting Author
Myeounghoon Cha
Poster Authors
Myeounghoon Cha
PhD
YONSEI UNIV COL MED
Lead Author
Heyji Bak
BS
Yonsei University College of Medicine
Lead Author
Sun Joon Bai
MD
Yonsei University College of Medicine
Lead Author
Bae Hwan Lee
Yonsei University College of Medicine
Lead Author
Jun Ho Jang
PhD
OV MEDI Co., Ltd
Lead Author
Topics
- Mechanisms: Biological-Systems (Physiology/Anatomy)