Nucleic acid aptamers capable of affine and specific binding to their molecular targets have now established themselves as a very promising alternative to monoclonal antibodies for diagnostic and therapeutic applications. Although the main focus in aptamers’ research and development for biomedicine is made on cardiovascular, infectious, and malignant diseases, the use of aptamers as therapeutic or diagnostic tools in the context of rheumatic diseases is no less important. In this review, we consider the main features of aptamers that make them valuable molecular tools for rheumatologists, and summarize the studies on the selection and application of aptamers for protein biomarkers associated with rheumatic diseases. We discuss the progress in the development of aptamer-based diagnostic assays and targeted therapeutics for rheumatic disorders, future prospects in the field, and issues that have yet to be addressed.

Osteoporosis is becoming a “silent pandemic” because of its ever-increasing prevalence and the absence of clinical manifestations until a bone fracture happens. The purpose of this review is to summarize the actual data on the pathogenesis of osteoporosis and its treatment options. The disease develops through a multifactorial process involving an imbalance between bone remodeling and different factors like genetics, non-coding RNA regulation, osteoimmune dysregulation, oxidative stress, cellular senescence, and fat–bone interactions. Existing medications have beneficial effects by preserving and increasing bone density and reducing the risk of fractures. Among them, there are bisphosphonates, strontium ranelate, calcitonin, estrogen-progestin therapy, selective estrogen receptor modulators, and parathyroid hormone analogues. Otherwise, they suffer from certain disadvantages, such as adverse effects, including serious ones, and limitations associated with comorbidity. Targeting pathways underlying bone metabolism could significantly improve the therapeutic options and provide new tools in the fight against osteoporosis. We consider here targeted therapeutics that are already in clinical practice, as well as the most promising novel agents that are now under development: antibodies, siRNAs, aptamers, and small molecules.

Chronic immunoinflammatory rheumatic diseases, such as axial spondyloarthritis (AxSpA), are accompanied by a dysregulation of bone remodeling. Among potential biomarkers of bone metabolism, the Wnt pathway antagonist, Dickkopf-1 (DKK-1), is of particular interest because of its potential to reflect a shift towards joint ossification or osteoporosis, but its diagnostic value needs validation. There is still a lack of stable and efficient methods of measuring serum DKK-1 levels suitable for longitude studies. The use of aptamer-based diagnostic assays could be very promising for this purpose. We generated novel anti-DKK-1 DNA aptamers from a combinatorial library with a pre-defined sequence pattern in the randomized region. This approach showed high efficacy, as only four SELEX rounds of selection produced high-affinity aptamers with dissociation constants ranging from 1.3 to 3.7 nM. A family of their truncated versions was also developed by rational design. Novel DNA aptamers functioned as capture components in a microplate ELISA-like assay with HRP-conjugated anti-DKK-1 antibody as a reporter component. We succeeded in revealing the aptamer/aptamer sandwich pairs that provided an aptamer-only sandwich colorimetric assay. The aptamer/antibody colorimetric test systems were also examined in the analyses of blood serum from AxSpA patients and shown sufficient workability. However, in a number of cases we registered significant differences between assays based on TD10 and DK4 aptamers and made some suggestions about the origin of this effect.

Ribozymes, DNAzymes, and fluorescent light-up aptamers combine sequence-programmable recognition with catalytic activity or ligand-dependent signal generation. Our review examines their functional diversity, current progress in studies of structure and mechanisms of action, and potential for analytical applications. Natural and in vitro-selected ribozymes and DNAzymes are considered in relation to phosphodiester-bond hydrolysis, ligation, phosphorylation/dephosphorylation, covalent modification, photochemical reactions, and peroxidase-like oxidation. Particular attention is given to the relationship between catalytic core architecture, substrate and cofactor positioning, metal ion coordination, nucleobase participation, and reaction mechanisms. We consider fluorescent aptamer–fluorogen pairs as analogs of catalytic nucleic acids, since they employ RNA or DNA structures to activate fluorescence through fluorogen immobilization, conformational restriction, or chemical transformation. Bioanalytical applications of ribozymes and DNAzymes include the detection of nucleic acids, viral RNA, metal ions, nucleotides, enzymes, pathogens, and small molecules, while aptamer/fluorogen pairs are particularly well-suited for fluorescence imaging of RNA and metabolites in living cells. The review highlights the growing integration of catalytic nucleic acids with amplification strategies, nanomaterials, aptamer domains, and optical or electrochemical reporters. Although functional diversity increases almost every year, structural information and comprehensive structure–function datasets remain limited. Future progress will depend on structural characterization, improved computational modeling, machine-learning-assisted design, and the development of robust, biocompatible systems for broad bioanalytical use.