Osteoarthritis afflicts millions of individuals across the world resulting in impaired quality of life and increased health costs. To understand this disease, physicians have been studying risk factors, such as genetic predisposition, aging, obesity, and joint malalignment; however have been unable to conclusively determine the direct etiology. Current treatment options are short-term or ineffective and fail to address pathophysiological and biochemical mechanisms involved with cartilage degeneration and the induction of pain in arthritic joints. OA pain involves a complex integration of sensory, affective, and cognitive processes that integrate a variety of abnormal cellular mechanisms at both peripheral and central (spinal and supraspinal) levels of the nervous system Through studies examined by investigators, the role of growth factors and cytokines has increasingly become more relevant in examining their effects on articular cartilage homeostasis and the development of osteoarthritis and osteoarthritis-associated pain. Catabolic factors involved in both cartilage degradation in vitro and nociceptive stimulation include IL-1, IL-6, TNF-α, PGE2, FGF-2 and PKCδ, and pharmacologic inhibitors to these mediators, as well as compounds such as RSV and LfcinB, may potentially be used as biological treatments in the future. This review explores several biochemical mediators involved in OA and pain, and provides a framework for the understanding of potential biologic therapies in the treatment of degenerative joint disease in the future.

Meniscal root tears, less common than meniscal body tears and frequently unrecognized, are a subset of meniscal injuries that often result in significant knee joint disorders. The meniscus root attachment aids meniscal function by securing the meniscus in place and allowing for optimal shock-absorbing function in the knee. With root tears, meniscal extrusion often occurs, and the transmission of circumferential hoop stresses is impaired. This alters knee biomechanics and kinematics and significantly increases tibiofemoral contact pressure. In recent years, meniscal root tears, which by definition include direct avulsions off the tibial plateau or radial tears adjacent to the root itself, have attracted attention because of concerns that significant meniscal extrusion dramatically inhibits normal meniscal function, leading to a condition biomechanically similar to a total meniscectomy. Recent literature has highlighted the importance of early diagnosis and treatment; fortunately, these processes have been vastly improved by advances in magnetic resonance imaging and arthroscopy. This article presents a review of the clinically relevant anatomic, biomechanical, and functional descriptions of the meniscus root attachments, as well as current strategies for accurate diagnosis and treatment of common injuries to these meniscus root attachments.

Objective. To elucidate the pathophysiologic links between prostaglandin E 2 (PGE 2 ) and osteoarthritis (OA) by characterizing the catabolic effects of PGE 2 and its unique receptors in human adult articular chondrocytes.Methods. Human adult articular chondrocytes were cultured in monolayer or alginate beads with and without PGE 2 and/or agonists of EP receptors, antagonists of EP receptors, and cytokines. Cell survival, proliferation, and total proteoglycan synthesis and accumulation were measured in alginate beads. Chondrocyte-related gene expression and phosphatidylinositol 3-kinase/Akt signaling were assessed by realtime reverse transcription-polymerase chain reaction and Western blotting, respectively, using a monolayer cell culture model.Results. Stimulation of human articular chondrocytes with PGE 2 through the EP2 receptor suppressed proteoglycan accumulation and synthesis, suppressed aggrecan gene expression, did not appreciably affect expression of matrix-degrading enzymes, and decreased the type II collagen:type I collagen ratio. EP2 and EP4 receptors were expressed at higher levels in knee cartilage than in ankle cartilage and in a grade-dependent manner. PGE 2 titration combined with interleukin-1 (IL-1) synergistically accelerated expression of painassociated molecules such as inducible nitric oxide synthase and IL-6. Finally, stimulation with exogenous PGE 2 or an EP2 receptor-specific agonist inhibited activation of Akt that was induced by insulin-like growth factor 1.Conclusion. PGE 2 exerts an antianabolic effect on human adult articular cartilage in vitro, and EP2 and EP4 receptor antagonists may represent effective therapeutic agents for the treatment of OA.

Osteoarthritis (OA) and degenerative disc disease (DDD) are similar diseases involving the breakdown of cartilage tissue, and a better understanding of the underlying biochemical processes involved in cartilage degeneration may allow for the development of novel biologic therapies aimed at slowing the disease process. Three members of the fibroblast growth factor (FGF) family, FGF-2, FGF-18, and FGF-8, have been implicated as contributing factors in cartilage homeostasis. The role of FGF-2 is controversial in both articular and intervertebral disc (IVD) cartilage as it has been associated with species- and age-dependent anabolic or catabolic events. Recent evidence suggests that FGF-2 selectively activates FGF receptor 1 (FGFR1) to exert catabolic effects in human articular chondrocytes and IVD tissue via upregulation of matrix-degrading enzyme production, inhibition of extracellular matrix (ECM) accumulation and proteoglycan synthesis, and clustering of cells characteristic of arthritic states. FGF-18, on the other hand, most likely exerts anabolic effects in human articular chondrocytes by activating the FGFR3 pathway, inducing ECM formation and chondrogenic cell differentiation, and inhibiting cell proliferation. These changes result in dispersed chondrocytes or disc cells surrounded by abundant matrix. The role of FGF-8 has recently been identified as a catabolic mediator in rat and rabbit articular cartilage, but its precise biological impact on human adult articular cartilage or IVD tissue remains unknown. The available evidence reveals the promise of FGF-2/FGFR1 antagonists, FGF-18/FGFR3 agonists, and FGF-8 antagonists (i.e., anti-FGF-8 antibody) as potential therapies to prevent cartilage degeneration and/or promote cartilage regeneration and repair in the future.

No abstract

The pathology of joint destruction is associated with elevated production of basic fibroblast growth factor (bFGF) and matrix metalloproteinase-13 (MMP-13). In osteoarthritic joint disease, expression of bFGF and MMP-13 in chondrocytes and their release into the synovial fluid are significantly increased. We have previously found that the capacity for cartilage repair in human adult articular chondrocytes is severely compromised by minimal exposure to bFGF because bFGF reduces responsiveness to bone morphogenetic protein-7 and insulin-like growth factor-1 and induces MMP-13 through protein kinase C␦-dependent activation of multiple mitogen-activated protein kinase (MAPK) signaling pathways. Here we show using biochemical and molecular approaches that transcription factor Elk-1, a direct downstream target of MAPK, is a critical transcriptional activator of of MMP-13 by bFGF in human articular chondrocytes. We also provide evidence that Elk-1 is a direct target of NFB and induces MMP-13 expression upon activation of the NFB signaling pathway. Taken together, our results suggest that elevated expression of MMP-13 occurs through Elk-1 activation of both MAPK and NFB signaling pathways, thus revealing a two-pronged biological mechanism by which bFGF controls the production of catabolic enzymes that are associated with excessive degradation of the cartilage matrix in degenerative joint diseases such as osteoarthritis.

In athletes, significant advances in anterior cruciate ligament reconstruction techniques and rehabilitation have led to improved surgical outcomes and increased expectations for return to play. Although an expeditious return to sport has become an achievable and often realistic goal, the factors that most influence safe, timely, and successful return to play remain unknown. The literature offers mainly anecdotal evidence to guide the team physician in the decision-making process, with a paucity of criteria and consensus guidelines available to help determine return to sport. Attempts have been made to introduce criteria-based progression in the rehabilitation process, but validation of subjective and objective criteria has been difficult. Nevertheless, several pertinent factors in the preoperative, intraoperative, and postoperative periods may affect return to play following anterior cruciate ligament reconstruction. Further research is warranted to validate reliable, consensus guidelines with objective criteria to facilitate the return to play process.

Quantitative descriptions of the anterior meniscal roots elucidate the relationship between the root attachments and pertinent surgical landmarks. In addition, the supplemental attachments of both menisci may contribute to native meniscal function, and further investigation is recommended.