The effects of metabolic syndrome, obesity, and the gut microbiome on load-induced osteoarthritis

Abstract

Severe obesity increased load-induced cartilage damage, while milder changes in adiposity/metabolic syndrome seen in TLR5KO mice did not. Furthermore, the effects of systemic inflammation/obesity on cartilage damage depend on the duration of mechanical loading. Lastly, reduced cartilage damage in the TLR5KOΔMicrobiota mice suggests that the gut microbiome may influence cartilage pathology.

Association between metabolic syndrome and hip osteoarthritis in middle-aged men and women from the general population

“…This might be explained due to the increased prevalence and radiological signs of knee osteoarthritis compared to hip osteoarthritis [31][32][33]. Furthermore, with being a weight bearing joint, the degenerative changes of the knee may primarily be caused by an increased mechanical load [8,16]. This was recently described in a mouse experiment, where severely obese mice had increased cartilage damage compared to metabolic mice with milder adiposity [8].…”

“…Osteoarthritis and metabolic syndrome are two of the leading disorders in developed countries [1][2][3][4][5]. Metabolic syndrome, a constellation of hazardous factors leading to diabetes mellitus as well as to cardiovascular disorders, contains common risk factors for both diseases such as increased blood glucose levels, elevated waist circumference (central obesity), elevated blood pressure, increased triglycerides and lowered HDL-c [5][6][7][8][9][10].…”

“…There are multiple risk factors for developing osteoarthritis of the weight bearing joints (e.g. knee or hip joint), such as age, nutritional habits or central obesity, which are concomitantly responsible for causing or worsening diabetes [1,4,8,10,15,16]. Yet, osteoarthritis and metabolic syndrome may simply be co-existing through these common risk factors [9,17].…”

Osteoarthritis and type 2 diabetes: From pathogenetic factors to therapeutic intervention

“…In a recent study, Guss et al compared OA severity, degree of systemic inflammation, and microbiota composition in high fat‐fed mice, which were knockout for the TLR5 gene with or without the administration of antibiotics. OA structural features and related inflammation were less severe in TLR5‐deficient mice after prolonged loading, being the lowest within the group treated with antibiotics, which showed the lowest diversity at the microbiota level with a preponderance of Proteobacteria over Bacteroides and Firmicutes . Main studies investigating the role of OB and inflammation in the pathogenesis of OA are summarized in Table .…”

“…OA structural features and related inflammation were less severe in TLR5-deficient mice after prolonged loading, being the lowest within the group treated with antibiotics, which showed the lowest diversity at the microbiota level with a preponderance of Proteobacteria over Bacteroides and Firmicutes. 113 Main studies investigating the role of OB and inflammation in the pathogenesis of OA are summarized in Table 4. Major mechanisms involving OB, metainflammation, and OA are depicted in Figure 3.…”