Radioactive xenon (133Xe) disappearance rates from the synovial cavity of the human knee joint in normal and arthritic subjects.

Onge, R A St; Dick, W C; Bell, G. H.; Boyle, J A

doi:10.1136/ard.27.2.163

Cited by 24 publications

(3 citation statements)

References 8 publications

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“…While investigating therapeutics that will suppress OA symptoms, numerous studies on intra-articular injections of nonsteroidal anti-inflammatory drugs have reported limited retention in synovial fluid and joint space. ,, Discovery of peptides that bind to specific ECM components of cartilage have paved the path for developing therapies that can be retained within the matrix. Here, we utilize biomolecular ligands that bind to HA and collagen type II to design and deliver molecules that adhere to an aggrecan depleted cartilage matrix.…”

Section: Discussionmentioning

confidence: 99%

Biomimetic Molecules Lower Catabolic Expression and Prevent Chondroitin Sulfate Degradation in an Osteoarthritic ex Vivo Model

Sharma

Vazquez-Portalatin

Calve

et al. 2016

ACS Biomater. Sci. Eng.

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Aggrecan, the major proteoglycan in cartilage, serves to protect cartilage tissue from damage and degradation during the progression of osteoarthritis (OA). In cartilage extracellular matrix (ECM) aggrecan exists in an aggregate composed of several aggrecan molecules that bind to a single filament of hyaluronan. Each molecule of aggrecan is composed of a protein core and glycosaminoglycan sides chains, the latter of which provides cartilage with the ability to retain water and resist compressive loads. During the progression of OA, loss of aggrecan is considered to occur first, after which other cartilage matrix components become extremely susceptible to degradation. Proteolytic cleavage of the protein core of aggrecan by enzymes such as aggrecanases, prevent its binding to HA and lower cartilage mechanical strength. Here we present the use of HA-binding or collagen type II-binding molecules that functionally mimic aggrecan but lack known cleavage sites, protecting the molecule from proteolytic degradation. These molecules synthesized with chondroitin sulfate backbones conjugated to hyaluronan-or collagen type IIbinding peptides, are capable of diffusing through a cartilage explant and adhering to the ECM of this tissue. The objective of this study was to test the functional efficacy of these molecules in an ex vivo osteoarthritic model to discern the optimal molecule for further studies. Different variations of chondroitin sulfate conjugated to the binding peptides were diffused through aggrecan depleted explants and assessed for their ability to enhance compressive stiffness, prevent CS degradation, and modulate catabolic (MMP-13 and ADAMTS-5) and anabolic (aggrecan and collagen type II) gene expression. A pilot in vivo study assessed the ability to retain the molecule within the joint space of an osteoarthritic guinea pig model. The results indicate chondroitin sulfate conjugated to hyaluronan-binding peptides is able to significantly restore equilibrium modulus and prevent CS degradation. All molecules demonstrated the ability to lower catabolic gene expression in aggrecan depleted explants. In order to enhance biosynthesis and regeneration, the molecules need to be coupled with an external stimulant such as a growth factor. The chondroitin sulfate molecule synthesized with HA-binding peptides demonstrated adherence to

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Section: Discussionmentioning

confidence: 99%

Biomimetic Molecules Lower Catabolic Expression and Prevent Chondroitin Sulfate Degradation in an Osteoarthritic ex Vivo Model

Sharma

Vazquez-Portalatin

Calve

et al. 2016

ACS Biomater. Sci. Eng.

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“…As apparent, relatively fast disappearance from the joint is observed for small solutes with t 1/2 values in the range of about 0.1 to 6 h. In this connection disappearance kinetics from the joint cavity has often been described by simple first‐order kinetics. However, several studies, for example,103–109 have found biphasic clearance patterns after IA injection, indicating the presence of a distribution phase associated with drug distribution from the SF to other joint tissues. An initial distribution phase is probably always present upon IA instillation but may or may not be observed depending on the study design.…”

Section: Drug Transport and Distribution Processes In A Synovial Envimentioning

confidence: 99%

Intra‐articular depot formulation principles: Role in the management of postoperative pain and arthritic disorders

Larsen

Østergaard

Larsen

et al. 2008

Journal of Pharmaceutical Sciences

251

212

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“…There is no way to measure synovial blood flow with confidence, although St. Onge, Dick, and their collaborators have developed and used the lssXe washout technique for this purpose (17)(18)(19)(20)(21)(22). This technique was first used by Phelps and McCarty as an empirical measurement of relative blood flow in inflamed animal joints (23).…”

Section: Synovial Blood Flowmentioning

confidence: 99%

Selected aspects of synovial membrane physiology

McCarty

1974

Arthritis & Rheumatism

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Radioactive xenon (133Xe) disappearance rates from the synovial cavity of the human knee joint in normal and arthritic subjects.

Cited by 24 publications

References 8 publications

Biomimetic Molecules Lower Catabolic Expression and Prevent Chondroitin Sulfate Degradation in an Osteoarthritic ex Vivo Model

Biomimetic Molecules Lower Catabolic Expression and Prevent Chondroitin Sulfate Degradation in an Osteoarthritic ex Vivo Model

Intra‐articular depot formulation principles: Role in the management of postoperative pain and arthritic disorders

Selected aspects of synovial membrane physiology

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