Osteoarthritis comprises several joint disorders characterized by articular cartilage degeneration and persistent pain, causing disability and economic burden. The incidence of osteoarthritis is rapidly increasing worldwide due to aging and obesity trends. Basic and clinical research on osteoarthritis has been carried out for decades, but many questions remain unanswered. The exact role of subchondral bone during the initiation and progression osteoarthritis remains unclear. Accumulating evidence shows that subchondral bone lesions, including bone marrow edema and angiogenesis, develop earlier than cartilage degeneration. Clinical interventions targeting subchondral bone have shown therapeutic potential, while others targeting cartilage have yielded disappointing results. Abnormal subchondral bone remodeling, angiogenesis and sensory nerve innervation contribute directly or indirectly to cartilage destruction and pain. This review is about bone-cartilage crosstalk, the subchondral microenvironment and the critical role of both in osteoarthritis progression. It also provides an update on the pathogenesis of and interventions for osteoarthritis and future research targeting subchondral bone.

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The objective of this study was to compare replacement of the radial head by metal prostheses with open reduction and internal fixation (ORIF) for the treatment of unstable, multi-fragmented radial head fractures. A prospective randomised controlled trial was employed to investigate 45 patients with unstable, multi-fragmented fractures of the radial head, from January 2004 to June 2007. The patients were randomised to two groups: the ORIF group and the radial head replacement group. Over the next two years, follow-up assessments recorded Broberg and Morrey scores and postoperative complication rate. Statistical analysis was performed. According to Broberg and Morrey scores, patients receiving radial head replacement achieved significantly better clinical results with 91% (20/22) good or excellent compared to patients assigned to the ORIF group with 65.2% (15/23) good or excellent results (P < 0.01). Postoperative complication rate of the radial head replacement group (13.6%) was significantly lower than that of the ORIF group (47.9%; P < 0.01). Compared with open reduction and internal fixation, radial head replacement with a metal prostheses resulted in favourable joint function for the unstable, multi-fragmented fractures of the radial head.

Osteoarthritis (OA) is the most common type of arthritis with no effective therapy. Subchondral bone and overlying articular cartilage are closely associated and function as “osteo-chondral unit” in the joint. Abnormal mechanical load leads to activated osteoclast activity and increased bone resorption in the subchondral bone, which is implicated in the onset of OA pathogenesis. Thus, inhibiting subchondral bone osteoclast activation could prevent OA onset. Betaine, isolated from the Lycii Radicis Cortex (LRC), has been demonstrated to exert anti-inflammatory, antifibrotic and antiangiogenic properties. Here, we evaluated the effects of betaine on anterior cruciate ligament transection (ACLT)-induced OA mice. We observed that betaine decreased the number of matrix metalloproteinase 13 (MMP-13)-positive and collagen X (Col X)-positive cells, prevented articular cartilage proteoglycan loss and lowered the OARSI score. Betaine decreased the thickness of calcified cartilage and increased the expression level of lubricin. Moreover, betaine normalized uncoupled subchondral bone remodeling as defined by lowered trabecular pattern factor (Tb.pf) and increased subchondral bone plate thickness (SBP). Additionally, aberrant angiogenesis in subchondral bone was blunted by betaine treatment. Mechanistically, we demonstrated that betaine suppressed osteoclastogenesis in vitro by inhibiting reactive oxygen species (ROS) production and subsequent mitogen-activated protein kinase (MAPK) signaling. These data demonstrated that betaine attenuated OA progression by inhibiting hyperactivated osteoclastogenesis and maintaining microarchitecture in subchondral bone.

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Abnormal subchondral bone remodeling featured by overactivated osteoclastogenesis leads to articular cartilage degeneration and osteoarthritis (OA) progression, but the mechanism is unclear. We used lymphocyte cytosolic protein 1 ( Lcp1 ) knockout mice to suppress subchondral osteoclasts in a mice OA model with anterior cruciate ligament transection (ACLT), and Lcp1 −/− mice showed decreased bone remodeling in subchondral bone and retarded cartilage degeneration. For mechanisms, the activated osteoclasts in subchondral bone induced type-H vessels and elevated oxygen concentration, which ubiquitylated hypoxia-inducible factor 1 alpha subunit (HIF-1α) in chondrocytes and led to cartilage degeneration. Lcp1 knockout impeded angiogenesis, which maintained hypoxia environment in joints and delayed the OA progression. Stabilization of HIF-1α delayed cartilage degeneration, and knockdown of Hif1a abolished the protective effects of Lcp1 knockout. Last, we showed that Oroxylin A, an Lcp1- encoded protein l -plastin (LPL) inhibitor, could alleviate OA progression. In conclusion, maintaining hypoxic environment is an attractive strategy for OA treatment.

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