Chondrocyte density, proteoglycan content and gene expressions from native cartilage are species specific and not dependent on cartilage thickness: a comparative analysis between rat, rabbit and goat

Kamisan, Norazian; Naveen, Sangeetha Vasudevaraj; Ahmad, Raja Elina; Kamarul, Tunku

doi:10.1186/1746-6148-9-62

Cited by 32 publications

(42 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…sGAG concentration measured for the different rat cartilages had a pooled mean concentration of 18.3 ± 6.0 µg/mg tissue wet weight, consistent with data reported by others in the literature . The sGAG contents for quadriceps tendon (5.8 ± 1.9 µg/mg), ligaments (4.1 ± 1.6 µg/mg), menisci (3.6 ± 0.2 µg/mg) and patella tendon (1.5 ± 0.4 µg/mg) were similar to that reported previously for rabbit and sheep .…”

Section: Resultssupporting

confidence: 89%

See 1 more Smart Citation

Electrostatic interactions enable rapid penetration, enhanced uptake and retention of intra‐articular injected avidin in rat knee joints

Bajpayee

Scheu

Grodzinsky

et al. 2014

Journal Orthopaedic Research

106

View full text Add to dashboard Cite

Intra-articular (i.a.) drug delivery for local treatment of osteoarthritis remains inadequate due to rapid clearance by the vasculature or lymphatics. Local therapy targeting articular cartilage is further complicated by its dense meshwork of collagen and negatively charged proteoglycans, which can prevent even nano-sized solutes from entering. In a previous in vitro study, we showed that Avidin, due to its size (7 nm diameter) and high positive charge (pI 10.5), penetrated the full thickness of bovine cartilage and was retained for 15 days. With the goal of using Avidin as a nano-carrier for cartilage drug delivery, we investigated its transport properties within rat knee joints. Avidin penetrated the full thickness of articular cartilage within 6 h, with a half-life of 29 h, and stayed inside the joint for 7 days after i.a. injection. The highest concentration of Avidin was found in cartilage, the least in patellar tendon and none in the femoral bone; in contrast, negligible Neutravidin (neutral counterpart of Avidin) was present in cartilage after 24 h. A positive correlation between tissue sGAG content and Avidin uptake (R 2 ¼ 0.83) confirmed the effects of electrostatic interactions. Avidin doses up to at least 1 mM did not affect bovine cartilage explant cell viability, matrix catabolism or biosynthesis. Keywords: Avidin; intra-articular drug delivery; rat; glycosaminoglycans; cartilage Osteoarthritis (OA) affects individual joints, necessitating localized therapy. 1,2 Intra-articular (i.a.) injections allow for local and targeted delivery of drugs into the joint space, thereby reducing systemic toxicity. However, i.a. therapy often remains inadequate due to rapid clearance of drugs from the joint space; small molecules exit via the vasculature while larger macromolecules (e.g., hyaluronan) are cleared by the lymphatic system. 2,3 Mean half-lives of NSAIDs in the synovial fluid have been reported to be 1-4 h. 4,5 Solutes in synovial fluid with sizes similar to plasma proteins (albumin $67 kDa, globulin $150 kDa, fibrinogen $340 kDa) have equal permeability through the lymphatics. 2 Their clearance, however, is dependent on the rate of synovial fluid turnover and solute diffusivity; the latter is a function of solute size and molecular weight, viscosity of synovial fluid and temperature. For example, intraarticular half-lives in normal rabbit knee joints have been reported to range from 0.23 h for Acridine Blue (370 Da) to 1.23 h for Albumin (67 kDa) and 26.3 h for Hyaluronan (300 kDa). 2,3 Intra-articular injection of drug-encapsulating particles can increase half-lives of therapeutic drugs in the synovial fluid. 1,6,7 However, therapeutic efficacy depends on the ability of the drugs (or particle-bound drugs) to penetrate into specific target tissues and to be retained by those tissues over time. Entry of macromolecules into cartilage is hindered by its dense extracellular matrix (ECM) of collagen fibrils and aggrecan proteoglycans containing highly negatively charged glycosaminoglycan (GAG) chai...

show abstract

Section: Resultssupporting

confidence: 89%

“…The diffusion‐binding time constant scales as the square of the thickness, so the transport rate into and out of rat cartilage is expected to be 100 times faster. An animal model having a thicker cartilage like rabbit or goat will be a closer representation of human physiology and transport kinetics.…”

Section: Discussionmentioning

confidence: 99%

Electrostatic interactions enable rapid penetration, enhanced uptake and retention of intra‐articular injected avidin in rat knee joints

Bajpayee

Scheu

Grodzinsky

et al. 2014

Journal Orthopaedic Research

106

View full text Add to dashboard Cite

show abstract

“…Both the size of the joint space and the thickness of soft tissues (cartilage, menisci, ligaments, tendons) increase with overall animal size. 17,18 For example, the following mean thickness values of articular cartilage for various mature animal species have been reported: mouse $50 mm, rat $100-150 mm, rabbit $350-700 mm, goat $900 mm, pig $1.5 mm, horse $1.5-2 mm and human $1.5-2 mm. [17][18][19][20][21] In this study, we demonstrate the significance of using animals larger than rodents for investigation of tissue-targeted intra-articular (i.a.)…”

Section: Introductionmentioning

confidence: 99%

A rabbit model demonstrates the influence of cartilage thickness on intra‐articular drug delivery and retention within cartilage

Bajpayee

Scheu

Grodzinsky

et al. 2015

Journal Orthopaedic Research

View full text Add to dashboard Cite

For evaluation of new approaches to drug delivery into cartilage, the choice of an animal model is critically important. Since cartilage thickness varies with animal size, different levels of drug uptake, transport and retention should be expected. Simple intra-articular injection can require very high drug doses to achieve a concentration gradient high enough for drug diffusion into cartilage. New approaches involve nanoparticle delivery of functionalized drugs directly into cartilage; however, diffusion-binding kinetics proceeds as the square of cartilage thickness. In this study, we demonstrate the necessity of using larger animals for sustained intra-cartilage delivery and retention, exemplified by intra-articular injection of Avidin (drug-carrier) into rabbits and compared to rats in vivo. Penetration and retention of Avidin within cartilage is greatly enhanced by electrostatic interactions. Medial tibial cartilage was the thickest of rabbit cartilages, which generated the longest intra-cartilage half-life of Avidin (t 1/2 ¼ 154 h). In contrast, Avidin half-life in thinner rat cartilage was 5-6 times shorter (t 1/2 $ 29 h). While a weak correlation (R 2 ¼ 0.43) was found between Avidin halflives and rabbit tissue GAG concentrations, this correlation improved dramatically (R 2 ¼ 0.96) when normalized to the square of cartilage thickness, consistent with the importance of cartilage thickness to evaluation of drug delivery and retention. ß

show abstract

“…After the article was published [1], we became aware that the name of our corresponding author was not correct. It should have been Tunku Kamarul [2,3] AND NOT Kamarul Tunku.…”

Section: Correctionmentioning

confidence: 99%

Erratum to: Chondrocyte density, proteoglycan content and gene expressions from native cartilage are species specific and not dependent on cartilage thickness: a comparative analysis between rat, rabbit and goat

et al. 2013

Self Cite

View full text Add to dashboard Cite

Chondrocyte density, proteoglycan content and gene expressions from native cartilage are species specific and not dependent on cartilage thickness: a comparative analysis between rat, rabbit and goat

Cited by 32 publications

References 32 publications

Electrostatic interactions enable rapid penetration, enhanced uptake and retention of intra‐articular injected avidin in rat knee joints

Electrostatic interactions enable rapid penetration, enhanced uptake and retention of intra‐articular injected avidin in rat knee joints

A rabbit model demonstrates the influence of cartilage thickness on intra‐articular drug delivery and retention within cartilage

Erratum to: Chondrocyte density, proteoglycan content and gene expressions from native cartilage are species specific and not dependent on cartilage thickness: a comparative analysis between rat, rabbit and goat

Contact Info

Product

Resources

About