Insights into osteoarthritis development from single-cell RNA sequencing of subchondral bone

• Published in: Rheumatic & musculoskeletal diseases open 2022-12, Vol.8 (2), p.e002617
• Main Authors: Shen, Ping, Löhning, Max
• Format: Article
• Language: English
• Subjects: Angiogenesis; Arthritis; Bone marrow; Calcification; Cartilage; Chondrocytes; Collagen; Homeostasis; Humans; Inflammation; Joint and ligament injuries; Osteoarthritis; Osteoarthritis - diagnosis; Osteoarthritis - genetics; Pathogenesis; Sequence Analysis, RNA; Vascular endothelial growth factor
• ISSN: 2056-5933; 2056-5933
• DOI: 10.1136/rmdopen-2022-002617

[...]OA is also a leading cause of disability, particularly among the elderly: an estimated 10%–15% of all adults aged over 60 years suffer from a certain degree of OA.1 2 Obesity, joint misalignment and joint injury are key risk factors for OA.3 It is estimated that at present 300 million people worldwide are affected by OA,4 and the number is expected to increase by about 50% in the next decade, as a result of the ageing of the global population as well as increasing obesity and joint injuries.5 Current treatments of OA cause very high costs of healthcare, but they are not able to effectively arrest or even slow down the degeneration process of joints.1 A more comprehensive understanding of the pathologic cellular and molecular mechanisms that drive OA development is still urgently needed for developing effective OA therapies. [...]a decade ago, Lories and Luyten referred to OA as ‘a disease of the whole joint’6 because the pathologic changes in OA joints include articular cartilage (AC) degradation, subchondral bone (SB) thickening (sclerosis), osteophyte formation, ligament and meniscus degeneration, synovial inflammation and the abnormality of other supporting tissue surrounding the joint capsule.7 Although AC degradation has long been considered the main cause of OA, accumulating evidence suggests that the structural alterations of SB also play an important role in the development and progression of OA. The architecture of SB varies by physiological regions, from the more compact layer adjacent to the calcified cartilage (SB plate) to the subchondral trabecular bone close to the medullary cavity.8 During physical movement, SB attenuates forces penetrated through cartilage, with the compact SB plate providing firm support and the compliance of SB trabecular module providing elasticity for shock absorption.8 SB abnormality is highly correlated with cartilage degeneration in both animals studied in OA models and humans with OA.9 Consistently, the improvement of the SB quality resulted in reduced AC degeneration, strongly suggesting that a normal SB structure is essential for maintaining the homeostasis of AC.6 10 Moreover, a recent study demonstrated that, during joint movement, SB reacts with counterforce to AC and through transforming growth factor beta (TGFβ) release, which plays an important role in regulating AC homeostasis and thus OA development.11 As AC and SB are directly attached to each other, the pathogenesis of AC also has significant impac