Therapeutic effects of MSCs, genetically modified MSCs, and NFĸB-inhibitor on chronic inflammatory osteolysis in aged mice.
Junichi KushiokaMasakazu ToyaHuaishuang ShenHirohito HirataNing ZhangEjun HuangMasanori TsubosakaQi GaoVictoria TeissierXueping LiTakeshi UtsunomiyaStuart B GoodmanPublished in: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (2022)
The number of total joint replacements is increasing, especially in elderly patients, and so too are implant-related complications such as prosthesis loosening. Wear particles from the prosthesis induce a chronic inflammatory reaction and subsequent osteolysis, leading to the need for revision surgery. This study investigated the therapeutic effect of NF-ĸB decoy oligodeoxynucleotides (ODN), mesenchymal stem cells (MSCs), and genetically-modified NF-ĸB sensing interleukin-4 over-secreting MSCs (IL4-MSCs) on chronic inflammation in aged mice. The model was generated by continuous infusion of contaminated polyethylene particles into the intramedullary space of the distal femur of aged mice (15-17 months old) for 6 weeks. Local delivery of ODN showed increased bone mineral density (BMD), decreased osteoclast-like cells, increased alkaline phosphatase (ALP)-positive area, and increased M2/M1 macrophage ratio. Local injection of MSCs and IL4-MSCs significantly decreased osteoclast-like cells and increased the M2/M1 ratio, with a greater trend for IL4-MSCs than MSCs. MSCs significantly increased ALP-positive area and BMD values compared with the control. The IL4-MSCs demonstrated higher values for both ALP-positive area and BMD. These findings demonstrated the therapeutic effects of ODN, MSCs, and IL4-MSCs on chronic inflammatory osteolysis in aged mice. The two MSC-based therapies were more effective than ODN in increasing the M2/M1 macrophage ratio, reducing bone resorption, and increasing bone formation. Specifically, MSCs were more effective in increasing bone formation, and IL4-MSCs were more effective in mitigating inflammation. This study suggests potential therapeutic strategies for treating wear particle-associated inflammatory osteolysis after arthroplasty in the elderly.
Keyphrases
- mesenchymal stem cells
- umbilical cord
- oxidative stress
- bone mineral density
- bone marrow
- cell therapy
- signaling pathway
- postmenopausal women
- lps induced
- low dose
- high fat diet induced
- nuclear factor
- pi k akt
- stem cells
- mass spectrometry
- type diabetes
- risk factors
- coronary artery bypass
- heavy metals
- climate change
- insulin resistance
- high speed