Page 12 - ISAKOS 2021 Newsletter Volume 1
P. 12

Preparing the Soil: Targeting Meta-Inflammation in Musculoskeletal Regenerative Medicine
By definition, meta-inflammation is a state of chronic inflammation mediated by macrophages that are present in certain locations such as the liver, muscle, adipose tissue, pancreas, colon, and brain2. These cells are known to coordinate immune activity and homeostasis, taking on different roles and displaying many cellular properties, depending on time and various biochemical stimuli2. Meta-inflammation can disrupt proper cell signaling and macrophage polarization, a process that also appears to be linked to MS. While meta-inflammation and disrupted cell signaling have been associated with MS and other autoimmune disorders, other unknowns still remain to be explored with regard to the origins and initiatory mechanisms of this disorder. In any case, this disorder still poses a great challenge for orthopaedic surgeons and other medical practitioners as chronic inflammation has been shown to harm musculoskeletal structures1. Musculoskeletal complications may be treated with conservative alternatives as well as novel therapeutic interventions such as the application of orthobiologics, which are regenerative therapies that are used to facilitate the healing of variety of tissues. Popular examples include hyaluronic acid, platelet-rich plasma, bone marrow, adipose tissue, and expanded mesenchymal stem cells3. In order to promote a more effective response, however, medical professionals must “prepare the soil” before managing a patient with an orthobiologic intervention. In other words, the target tissue must be biologically receptive to therapeutic agents. This goal can be achieved by designing health protocols that modulate an individual’s metabolic profile with the inclusion of dietary modifications, intermittent fasting, health supplements (minerals and vitamins), hormonal regulation, and other alternatives.
The objective of this review is to discuss some but not all of the known biologic soil-preparation alternatives in the fight against meta-inflammation, demonstrating the importance of primarily addressing low-grade chronic inflammation preceding interventional therapies.
Macrophage Polarization
The polarization of macrophages has been broadly divided into two distinct phenotypes (M1 and M2), which are attributed to the corresponding Th1 and Th2 (t helper) cell responses4. The M1 macrophages have been classically associated with inflammatory responses. These responses are usually mediated by certain inflammatory agents such as interferon- (IFN- ) and lipopolysaccharide (LPS), which allows these cells to develop microbicidal and proinflammatory properties, a main feature of this specific phenotype. M1 receptors for cytokines and LPS, in turn, allow signal transduction, which results in the expression of well-known inflammatory mediators such as inducible nitric oxide synthase (iNOS), tumor necrosis factor- (TNF- ), and chemokine (C-C motif) ligand 2 (CCL2/MCP-1)4.
Alberto Gobbi, MD
OASI Bioresearch Foundation Gobbi NPO Milan, ITALY
Gabriel Silva Santos, B.Sc
The Bone and Cartilage Institute, BRAZIL
Lucas Furtado da Fonseca, MD
The Bone and Cartilage Institute, BRAZIL
Jose Fabio Santos Duarte Lana, MD
The Bone and Cartilage Institute, BRAZIL
Gabriel Azzini, MD
The Bone and Cartilage Institute, BRAZIL
It is well known that the rise in metabolic syndrome (MS) has become a major health burden across the globe. Excessive caloric intake and poor dietary habits pave the way for the progression of “meta-inflammation,” which disrupts metabolic equilibrium and eventually aggravates low-grade chronic inflammation throughout the body1.

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