doi: 10.3390/children10061022 43
Injections of miR-141-3p agomir, miR-411 mimics, miR-9, miR-21 lentivirus, miR-26a, miRNA-147 mimics have been proven to ameliorate cartilage injury and bone erosion, further inhibiting inflammatory arthritic development in CIA animal models (223, 226, 229, 230, 284)
GLP-1 RAs effectively reduce appetite and caloric intake, yet unstructured reduced dietary intake is often nutrient poor and patients risk losing the fiber, polyphenols, and foods that sustain microbiome diversity, normobiosis, microbial mediators, and intestinal barrier function
Not only is TGF essential for maintenance of articular cartilage metabolic and structural homeostasis through regulating the expression of collagen type II and MMP13, the TGF signaling also seems to mediate Smad2/3 to facilitate osteoclastic differentiation and bone resorption, recruit nestin-positive MSCs and osteoprogenitors to resorption pits in subchondral bone, and promote osteoblast terminal maturation, depositing extracellular matrix components Col1 and osteocalcin in bone [117,122-124]
Single site mutations at asparagine residues were shown to result in a functionally active yet slightly less thermally stable version of the enzyme in vitro, while knockout of all asparagine residues resulted in an accumulation of the uncleaved, propeptide form of the enzyme
Clinical scenarios warranting consideration of GLP-1 therapy include: Type 2 diabetes management : Per ADA 2024 Standards of Care, GLP-1 RAs may be considered as initial therapy in patients with established atherosclerotic cardiovascular disease (ASCVD), high ASCVD risk, chronic kidney disease (CKD), or heart failure, or as add-on therapy when glycemic targets aren't met Established cardiovascular disease : Several GLP-1 receptor agonists have demonstrated cardiovascular risk reduction in patients with type 2 diabetes and established ASCVD Chronic kidney disease : While SGLT2 inhibitors are generally prioritized for CKD with type 2 diabetes when eGFR allows, GLP-1 RAs may provide complementary benefits Obesity with complications : When lifestyle interventions produce insufficient weight loss in patients with obesity-related comorbidities Important safety considerations include: Contraindications : Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
