Emerging targets in osteoarthritis therapy

Goldring, Mary B.; Bérenbaum, Francis

doi:10.1016/j.coph.2015.03.004

Cited by 147 publications

(130 citation statements)

References 198 publications

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“…Analysis of an age range of articular cartilage tissue sections revealed a trend toward decreased Dnmt3b expression with increasing age as shown by 2 representative IHC images (at 3 and 27 months old) ( Figure 1B). Surgical induction of OA in mice was carried out by meniscal ligament injury (MLI) (8) to destabilize the joint and induce articular cartilage degradation over time. Lower Dnmt3b expression levels were noted in articular chondrocytes 4 weeks following MLI compared with sham controls ( Figure 1C).…”

Section: Resultsmentioning

confidence: 99%

“…Many of the cellular and molecular changes in OA have been identified in studies utilizing murine models of OA or from analysis of human cartilage/chondrocytes from OA patients (6)(7)(8). As a result, there is the potential for development of new therapeutic approaches to target factors involved in inflammation, oxidative stress, and autophagy, to name a few (9).…”

Section: Introductionmentioning

confidence: 99%

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DNA methyltransferase 3b regulates articular cartilage homeostasis by altering metabolism

Shen¹,

Wang²,

Li³

et al. 2017

JCI Insight

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DNA methyltransferase 3b regulates articular cartilage homeostasis by altering metabolism

Shen¹,

Wang²,

Li³

et al. 2017

JCI Insight

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“…acetaminophen); (3) administer nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g. COX-2 inhibitors); (4) inject hyaluronic acid or corticosteroid into the intraarticular joint space; (5) total knee replacement [2]. However, these treatments fail to effectively alleviate symptoms for many patients [2].…”

Section: Discussionmentioning

confidence: 99%

“…COX-2 inhibitors); (4) inject hyaluronic acid or corticosteroid into the intraarticular joint space; (5) total knee replacement [2]. However, these treatments fail to effectively alleviate symptoms for many patients [2]. Many pharmaceutical companies have also recently closed research programs for OA due to the complexity of treatments and the difficulty in demonstrating their efficacy in clinical trials [29].…”

Section: Discussionmentioning

confidence: 99%

Knee Osteoarthritis Treated with Percutaneous Chondral-Bone Interface Optimization: A Pilot Trial

Vad¹,

Barve²,

Linnell³

et al. 2016

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Objective: The objective is to evaluate the efficacy of using tibial bone marrow delivered to the chondral-bone interface (CBI) via percutaneous chondral bone interface optimization (PeCaBoo) as a therapy for knee osteoarthritis (OA). Study Design: A series of prospective cases were presented. Participants: Our study included 10 patients with medial or lateral compartment knee OA. Methods: With 1 cc of heparin pre-loaded in the syringe, 5 cc of tibial bone marrow was withdrawn from the proximal tibia. The resultant 6 cc of aspirate in the syringe was injected via PeCaBoo, 2 cc at a time, into the superior CBI and inferior CBI. The remaining 2 cc was injected via needle into the intra-articular joint space. Main Outcome Measurements: Patients had MRIs taken pre-procedure and 3 months post-procedure to measure bone edema and intra-articular matrix thickness. Patient-reported outcomes recorded included the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the Numeric Paint Rating Scale (NRS), which were both obtained pre-procedure and post-procedure at 3, 6, and 12 months. Use of non-steroidal anti-inflammatories (NSAIDs) was recorded pre-and post-procedure as well. Results: Our study included 4 males and 6 females, with an average age of 63.5 years. The average follow-up time was 14 months, with a range of 13 -15 months. The mean WOMAC score was 58.2 points pre-procedure and 35.3 points post-procedure (p < 0.01). The mean NRS-Pain score was 8.6 points pre-procedure and 2.8 points post-procedure (p < 0.01). The matrix thickness increased by 14% on average at 3 months postprocedure (p < 0.01). The proportion of patients taking NSAIDs decreased by 60% after the PeCaBoo procedure. The subgroup of patients with tibial edema and knee OA had optimal outcomes. Conclusions: Tibial bone marrow stem cell delivered via PeCaBoo is a novel minimally-invasive treatment for knee OA, with potential to repair cartilage and improve knee pain and function. * Corresponding author. V. Vad et al.2

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“…1). While new targets are emerging to treat osteo-arthritis [1], palliative treatments with non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroid injections remain the most common therapies. Eventually, hip and knee replacement become necessary in many patients.…”

mentioning

confidence: 99%

An osteoarthritis triple play

Luft

2016

J Mol Med

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In American baseball, a triple play is the rare act of making three outs during the same continuous play. In this issue of J Mol Med, we feature a triple play against the world's most common disease. Osteoarthritis (OA) is a degenerative joint disease and the commonest form of arthritis affecting about one third of adults over age 45 years. Since most of these persons seek medical treatment, osteoarthritis is a massive worldwide healthcare and financial burden. Articular cartilage loss, subchondral bone thickening, and osteophyte formation characterize the condition. A cartoon outlining the process is shown (Fig. 1). While new targets are emerging to treat osteo-arthritis [1], palliative treatments with non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroid injections remain the most common therapies. Eventually, hip and knee replacement become necessary in many patients. Furthermore, much back surgery is a sequel to OA. Not uncommonly, physicians prescribe opioids, such as oxycodone when NSAIDs fail. As a result, osteoarthritis is a major contributor to the entire pain industry.OA is associated with many contributing factors including aging, obesity, trauma, genetics, and other accompanying causes; however, basic molecular mechanisms are not fully understood. Debate remains as to what is really the precipitating pathology, since everyone eventually has OA. Poulet and Staines have underscored the focus on different joint tissues affected by OA, including a focus on articular cartilage maintenance, targeting subchondral bone, inhibiting osteoclast activity, modifying osteoblast behavior, and adjusting angiogenesis [2].Moon et al. recently reported in this journal that mice lacking pannexin 3 (Panx3) specifically in cartilage were markedly resistant to the development of OA following destabilization after medial meniscus surgery [3]. Their data indicated a specific catabolic role of Panx3 in articular cartilage maintenance and identified Panx3 as a potential therapeutic target for OA. Their report was the first in vivo evidence for a role of Panx3 in disease. Since three additional investigations into OA are reported by this journal following the paper by Moon and colleagues, examining the subject again appears highly justified.Ko and colleagues also concerned themselves with articular cartilage maintenance [4]. They point out that heat-shock proteins (HSPs), intracellular chaperones, orchestrate tissue homeostasis and are important in remodeling and repair. They studied the articular cartilage from OA patients undergoing knee surgery and found reduced HSP60 concentrations in cartilage and synovial fluid compared to specimens from non-OA patients. Furthermore, expression of the SRY-box 9 (SOX9) chondrogenic transcription factor was reduced. They next investigated chondrocyte cultures that were stimulated with interleukin-1β (IL-1β). This exposure reduced HSP60, SOX9, collagen II, and aggrecan expression; however, the reductions were ameliorated when HSP60 was restored. To pursue the issue further, the i...

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Emerging targets in osteoarthritis therapy

Cited by 147 publications

References 198 publications

DNA methyltransferase 3b regulates articular cartilage homeostasis by altering metabolism

DNA methyltransferase 3b regulates articular cartilage homeostasis by altering metabolism

Knee Osteoarthritis Treated with Percutaneous Chondral-Bone Interface Optimization: A Pilot Trial

An osteoarthritis triple play

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