Pascal Richette

Calcium-containing crystal deposition diseases are extremely common in rheumatology. However, they are under-explored compared to gout or other inflammatory rheumatic diseases. Major advances have been made in 2023 that will undoubtedly stimulate and facilitate research in the field of calcium pyrophosphate (CPP) deposition disease (CPPD): the ACR/EULAR classification criteria for CPPD and a semi-quantitative OMERACT score for ultrasound assessment of the extent of CPP deposition have been validated and published. A large randomized controlled trial compared the efficacy and safety of colchicine and prednisone in acute CPP arthritis. Preclinical studies have elucidated the pro-inflammatory and anti-catabolic effects of basic calcium phosphate (BCP) crystals on mononuclear cells and chondrocytes. The association between osteoarthritis (OA) and IA calcifications has been the subject of several epidemiological publications, suggesting that calcium crystals are associated with a greater risk of progression of knee OA. Research in the field of calcium crystal deposition diseases is active: the areas of investigation for the coming years are broad and promising.

Articular cartilage has low regenerative capacity despite permanent stress. Irreversible cartilage lesions characterize osteoarthritis (OA); this is not followed by tissue repair. Lin28a, an RNA binding protein, is detected in damaged cartilage in humans and mice. We investigated the role of LIN28a in cartilage physiology and in osteoarthritis. Lin28a-inducible conditional cartilage deletion up-regulated Mmp13 in intact mice and exacerbated the cartilage destruction in OA mice. Lin28a-specific cartilage overexpression protected mice against cartilage breakdown, stimulated chondrocyte proliferation and the expression of Prg4 and Sox9, and down-regulated Mmp13 . Lin28a overexpression inhibited Let-7b and Let-7c miRNA levels while RNA-sequencing analysis revealed five genes of transcriptional factors regulated by Let-7. Moreover, Lin28a overexpression up-regulated HMGA2 and activated SOX9 transcription, a factor required for chondrocyte reprogramming. HMGA2 siRNA knockdown inhibited the cartilage protective effect of Lin28a overexpression. This study provides insights into a new pathway including the Lin28a-Let7 axis, thus promoting chondrocyte anabolism in injured cartilage in mice.