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New Challenges in Intra-articular Treatments
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New Challenges in Intra-articular Treatments

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 10377

Special Issue Editors

Prof. Dr. Giovanni Iolascon

E-Mail Website
Guest Editor
Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, Via De Crecchio 4, 80138 Naples, Italy
Interests: vitamin D; osteoporosis; sarcopenia; CRPS; musculoskeletal pain; neuromuscular diseases; lysosomal storage disorders
Special Issues, Collections and Topics in MDPI journals
Dr. Alberto Migliore

E-Mail Website
Guest Editor
Rheumatology Department, San Pietro Hospital Fatebenefratelli, 00189 Rome, Italy
Interests: injections; intra-articular; hyaluronic acid; viscosupplementation; osteoarthritis; hip; cartilage regeneration; corticosteroid injection

Special Issue Information

Dear Colleagues,

Osteoarthritis is the most common degenerative joint disease and age-related condition in Western countries, resulting in significant pain, functional limitation, and poor social participation and quality of life. Despite its huge prevalence and economic burden, no curative intervention for osteoarthritis has been developed so far. Intra-articular injections of various agents are commonly prescribed to treat this condition, with conflicting evidence. On the other hand, an era of relevant scientific development is emerging in this therapeutic field, considering the improved knowledge of physiopathological pathways, the advances in the characterization of biomolecules, the increasing use of drugs previously administrated only through systemic routes and for which the opportunity of intra-articular treatment was foreseen, and the progress of precision medicine. The scope of this Special Issue is to critically underline perspectives and challenges of innovative intra-articular approaches.

Prof. Dr. Giovanni Iolascon
Dr. Alberto Migliore
Guest Editors

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Keywords

  • injections
  • intra-articular
  • hyaluronic acid
  • viscosupplementation
  • tribosupplementation
  • biological products
  • intra-articular niche cells
  • osteoarthritis
  • clodronic acid

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Published Papers (3 papers)

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Research

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19 pages, 2806 KiB  
Article
Quadruped Gait and Regulation of Apoptotic Factors in Tibiofemoral Joints following Intra-Articular rhPRG4 Injection in Prg4 Null Mice
by Daniel S. Yang, Edward E. Dickerson, Ling X. Zhang, Holly Richendrfer, Padmini N. Karamchedu, Gary J. Badger, Tannin A. Schmidt, Alger M. Fredericks, Khaled A. Elsaid and Gregory D. Jay
Int. J. Mol. Sci. 2022, 23(8), 4245; https://doi.org/10.3390/ijms23084245 - 12 Apr 2022
Cited by 4 | Viewed by 3389
Abstract
Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome leads to diarthrodial joint arthropathy and is caused by the absence of lubricin (proteoglycan 4—PRG4), a surface-active mucinous glycoprotein responsible for lubricating articular cartilage. In this study, mice lacking the orthologous gene Prg4 served as a model that recapitulates [...] Read more.
Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome leads to diarthrodial joint arthropathy and is caused by the absence of lubricin (proteoglycan 4—PRG4), a surface-active mucinous glycoprotein responsible for lubricating articular cartilage. In this study, mice lacking the orthologous gene Prg4 served as a model that recapitulates the destructive arthrosis that involves biofouling of cartilage by serum proteins in lieu of Prg4. This study hypothesized that Prg4-deficient mice would demonstrate a quadruped gait change and decreased markers of mitochondrial dyscrasia, following intra-articular injection of both hindlimbs with recombinant human PRG4 (rhPRG4). Prg4−/− (N = 44) mice of both sexes were injected with rhPRG4 and gait alterations were studied at post-injection day 3 and 6, before joints were harvested for immunohistochemistry for caspase-3 activation. Increased stance and propulsion was shown at 3 days post-injection in male mice. There were significantly fewer caspase-3-positive chondrocytes in tibiofemoral cartilage from rhPRG4-injected mice. The mitochondrial gene Mt-tn, and myosin heavy (Myh7) and light chains (Myl2 and Myl3), known to play a cytoskeletal stabilizing role, were significantly upregulated in both sexes (RNA-Seq) following IA rhPRG4. Chondrocyte mitochondrial dyscrasias attributable to the arthrosis in CACP may be mitigated by IA rhPRG4. In a supporting in vitro crystal microbalance experiment, molecular fouling by albumin did not block the surface activity of rhPRG4. Full article
(This article belongs to the Special Issue New Challenges in Intra-articular Treatments)
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12 pages, 3511 KiB  
Article
Hyaluronic Acid as a Carrier Supports the Effects of Glucocorticoids and Diminishes the Cytotoxic Effects of Local Anesthetics in Human Articular Chondrocytes In Vitro
by Lukas B. Moser, Christoph Bauer, Vivek Jeyakumar, Eugenia-Paulina Niculescu-Morzsa and Stefan Nehrer
Int. J. Mol. Sci. 2021, 22(21), 11503; https://doi.org/10.3390/ijms222111503 - 25 Oct 2021
Cited by 7 | Viewed by 2738
Abstract
The current study aimed to investigate the cytotoxicity of co-administrating local anesthetics (LA) with glucocorticoids (GC) and hyaluronic acid (HA) in vitro. Human articular cartilage was obtained from five patients undergoing total knee arthroplasty. Chondrocytes were isolated, expanded, and seeded in 24-well plates [...] Read more.
The current study aimed to investigate the cytotoxicity of co-administrating local anesthetics (LA) with glucocorticoids (GC) and hyaluronic acid (HA) in vitro. Human articular cartilage was obtained from five patients undergoing total knee arthroplasty. Chondrocytes were isolated, expanded, and seeded in 24-well plates for experimental testing. LA (lidocaine, bupivacaine, ropivacaine) were administered separately and co-administered with the following substances: GC, HA, and GC/HA. Viability was confirmed by microscopic images, flow cytometry, metabolic activity, and live/dead assay. The addition of HA and GC/HA resulted in enhanced attachment and branched appearance of the chondrocytes compared to LA and LA/GC. Metabolic activity was better in all LA co-administered with HA and GC/HA than with GC and only LA. Flow cytometry revealed the lowest cell viability in lidocaine and the highest cell viability in ropivacaine. This finding was also confirmed by live/dead assay. In conclusion, HA supports the effect of GC and reduces chondrotoxic effects of LA in vitro. Thereby, the co-administration of HA to LA and GC offers an alternative less chondrotoxic approach for treating patients with symptomatic osteoarthritis of the knee. Full article
(This article belongs to the Special Issue New Challenges in Intra-articular Treatments)
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Review

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16 pages, 935 KiB  
Review
The Rationale for the Intra-Articular Administration of Clodronate in Osteoarthritis
by Antimo Moretti, Marco Paoletta, Sara Liguori, Walter Ilardi, Francesco Snichelotto, Giuseppe Toro, Francesca Gimigliano and Giovanni Iolascon
Int. J. Mol. Sci. 2021, 22(5), 2693; https://doi.org/10.3390/ijms22052693 - 7 Mar 2021
Cited by 15 | Viewed by 3436
Abstract
Background: Several pharmacological therapeutic approaches have been proposed to manage osteoarthritis (OA), including intra-articular (IA) injections. Although the discovery of clodronate, a bisphosphonate, dates back to the 1960s and the effects of its IA administration have been investigated for decades in animal models, [...] Read more.
Background: Several pharmacological therapeutic approaches have been proposed to manage osteoarthritis (OA), including intra-articular (IA) injections. Although the discovery of clodronate, a bisphosphonate, dates back to the 1960s and the effects of its IA administration have been investigated for decades in animal models, mechanisms of action of this drug are not quite clear, particularly in OA. This scoping review is an overview of the biological as well as the clinical role of clodronic acid in OA. Method: A scoping review based on the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model was performed to characterize the mechanisms of action of IA clodronate in OA and to evaluate its efficacy from a clinical point of view. Results: Several effects of clodronate have been observed in animal models of OA, including depletion of synovial lining cells that results in reduced production of chemokines (IL-1, TNF- α), growth factors (TGF-β, BMP 2/4), and metalloproteases (MMP 2/3/9); prevention of cartilage damage, synovial hyperplasia, and proteoglycans loss; reduction in joint inflammation, joint swelling, and osteophyte formation. From a clinical perspective, patients with knee OA treated with IA clodronate experienced improvements in pain and joint mobility. Conclusion: Clodronate appears to have different mechanisms of action interfering with the pathogenic processes contributing to OA development and progression. This intervention demonstrated positive effects for patients affected by knee OA. Full article
(This article belongs to the Special Issue New Challenges in Intra-articular Treatments)
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