Cindy Boer

44 | Chapter 1.2 Table 2: Selected miRNAs With Effects on Bone or Osteoarthritis Shown in Loss‐of‐Function or Gain‐of‐ Function Experiments In Vivo Positive effects on bone formation or bone mass [ref.] Negative effects on bone formation or bone mass [ref.] Amelioration of osteoarthritis [ref.] Aggravation of osteoarthritis [ref.] miR‐135 [147] miR‐103 [148] miR‐140‐5p [149] miR‐101 [150] miR‐141 [151] miR‐125b [152] miR‐142‐3p [153] miR‐181a‐5p [138] miR‐145 a [154] miR‐133 [155] miR‐210‐5p [156] miR‐221 [157] miR‐148 [158] miR‐138‐5p [159] miR‐370 [160] miR‐199a‐5p [161] miR‐140 [76] miR‐373 [160] miR‐21 a [74] miR‐145a [162] miR‐98 [163] miR‐216a [164] miR‐146 [165] miR‐26a a [166] miR‐148 [167] miR‐29b‐3p [168] miR‐208 [169] miR‐335 [77] miR‐21 a [170] miR‐34a‐5p [171] miR‐214‐3p [66] miR‐503 [172] miR‐222 [75] miR‐286 [167] miR‐23b [173] miR‐375 [174] miR‐26a a [175] miR‐31‐5p [78] miR‐341 [76] miR‐3831 [77] A Some miRNAs have shown contradictory effects in different models. Use of miRNAs to diagnose and treat disease The translational potential of miRNAs is large, since they can potentially be used to directly treat disease. A number of miRNAs enhance the osteogenic differentiation of MSCs; hence, they have been pointed out as potential therapies to promote bone regen- eration. For example, scaffolds and particles loaded with analogs of miR‐21 or miR‐148 potentiate bone regeneration in experimental models, at least in part, by interacting with the RUNX2 pathway[73, 74]. On the other hand, anti‐sense oligonucleotides and “sponges” inhibiting miR‐22, miR‐29, miR‐31, miR‐133, miR‐138, or miR‐214 have a stimulatory effect on osteogenesis and may improve fracture healing[62, 75, 76]. Also, miRNA‐engineered MSCs may find a role in bone regeneration[77, 78]. miRNA‐based therapies have also been explored in joint disorders. In this view, the intra‐articular injection of lentiviruses expressing miR‐140 and miR‐210 ameliorated joint disease in experimental models of OA[79]. Many cells can secrete miRNAs (mainly via exosomes) that are detectable in the synovial fluid and the circulation. Hence, several miRNAs have been suggested as poten- tial biomarkers for the diagnosis or follow‐up of skeletal disorders (see recent reviews)