Page 14 - ISAKOS 2021 Newsletter Volume 1
P. 14

Preparing the Soil: Targeting Meta- Inflammation in Musculoskeletal Regenerative Medicine
Its anabolic effects on bone cartilage have been well described for decades. Its ability to regulate the maintenance and recovery of muscle mass may have a direct impact on the outcomes of various therapies. To elaborate, low testosterone levels in both men and women lead to an increase in muscle catabolism and an increase in body fat deposition.
Testosterone stimulation increases the proliferation and preservation of stemness of MSCs and endothelial progenitor cells (EPCs), which indicates that, in addition to other factors, this anabolic steroid hormone may guide these cells and increase their therapeutic potential. Similarly, dehydroepiandrosterone (DHEA) appears to antagonize catabolic mediators of cartilage and may display protective effects in OA, including the inhibition of matrix metalloproteinases (MMPs) while favoring cartilage restoration. Actually, DHEA’s positive effects on OA may be attributed to its ability to influence the balance between the aggrecanases and tissue inhibitors of metalloproteinase-3 (TIMP-3) in chondral tissues, suggesting a suitable role in protecting articular cartilage from degeneration at the molecular level. Estrogens should not be dismissed, either. The absence or insufficient concentration of this hormone causes elevated bone resorption, thereby allowing the establishment of osteoporosis-like phenotype and aggravation of microscopic OA features that develop in both sexes.
Dietary Modifications
Perhaps one of the most obvious and least expensive strategies to fight meta-inflammation is to place the patient on a specific dietary regimen. Adequate diet is extremely important for bone and cartilage health, particularly when it comes to the comparison of fat and carbohydrate content in specific meal plans. For instance, bone formation appears to be increased in high-fat diets as a result of osteoblast activity, at least in rats. Conversely, high concentrations of sugar in specific diets may promote bone marrow adipose expansion and the subsequent alteration of the bone marrow microenvironment. This is also accompanied by the shift toward a more pro-inflammatory microenvironment, which could have additional detrimental effects on bone metabolism and musculoskeletal health.
Further expanding on carbohydrates, fructose consumption also can reduce the osteogenic potential of stromal cells in the bone marrow and can increase the adipogenic differentiation tendency, which is particularly harmful to the bone microarchitecture.
MS-derived inflammation is strongly associated with a higher prevalence of symptomatic knee OA as well as with higher serum interleukin (IL)-6 and tumor necrosis factor (TNF)-R2 levels, suggesting that there is a close relationship between diet and inflammatory parameters that culminates in the progression of OA.
A viable solution for this problem is the inclusion of the anti-inflammatory Mediterranean diet, which is known for its positive effects in the management of symptoms. Individuals who adhere to this dietary habit may exhibit far less prevalence of knee OA in comparison to those who do not. The Mediterranean-style diet is an established healthy- eating diet pattern that seems to convey beneficial effects on metabolic, cardiovascular, musculoskeletal, and cognitive diseases. It also may be partially responsible for a reduction in oxidative stress markers and the promotion of elevated levels of type-II collagen and aggrecan expression, while inhibiting apoptosis-related protein synthesis.
Gut Health
The intestinal flora are known to be a key regulator of bone health, affecting postnatal skeletal development and skeletal involution, for instance. Alterations in bacterial populations and host responses to the gut microbiome may collectively contribute to negative reactions resulting in bone loss. The positive alterations in microbiota composition that help to prevent and even reverse bone loss can be generated via the incorporation of nutritional supplements into a diet plan, especially those that are enriched with prebiotics and probiotics (Fig. 1). By definition, probiotics are viable microorganisms that confer health benefits when administered in adequate quantities. Prebiotics, in turn, are non-digestible fermentable food ingredients that stimulate the growth of benevolent microbes and promote beneficial changes in the gut microbiome behavior. This is a particularly important strategy as the gut microbiome regulates bone mineral density.
01 Nutritional supplementation with prebiotics and probiotics that increase the biosynthesis of SCFA production in combination with the regular practice of physical activity may represent an effective, safe, and inexpensive alternative for the improvement of musculoskeletal regenerative medicine.

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