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Research:
L. R. Goodrich, C. Hidaka, P. D. Robbins, C. H. Evans, and A. J. Nixon
Genetic modification of chondrocytes with insulin-like growth factor-1 enhances cartilage healing in an equine model
J Bone Joint Surg Br 2007; 89-B: 672-685 [Abstract] [Full text] [PDF]
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[Read eLetter] Genetic modification of chondrocytes with insulin-like growth factor-1
Benedict A Rogers, NJ Little   (5 July 2007)

Genetic modification of chondrocytes with insulin-like growth factor-1 5 July 2007
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Benedict A Rogers,
Specialist Registrar
South West Thames,
NJ Little

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Re: Genetic modification of chondrocytes with insulin-like growth factor-1

benedictrogers{at}hotmail.com Benedict A Rogers, et al.

Sir,

We read this paper with interest and would like to make the following points:

1. There are significant inter-species variations in the intrinsic mechanical properties of distal femoral cartilage.1 In a tissue that is load sensitive, care must be taken when extrapolating the results of cartilage healing to other species. Furthermore, since the patello-femoral joint in the human may experience up to five times body weight,2 detail of the weights of the horses used would be informative.

2. The study utilises a scoring system to evaluate the gross cartilage lesions (Table 1). Clinicians use either the Outerbridge or International Cartilage Research Society (ICRS) grading scoring systems when analysing osteochondral defects, for both patient management and research. Can the results from this study, using a different scoring system, be correlated with these more commonly used scoring systems?

3. The histological changes observed in this study in response to AdIGF-1, whilst significant, may not represent its primary effect. The regulation of collagen II mRNA expression is likely to be multifactorial and linked with proteoglycan synthesis. Since proteoglycans provide the principal osmotic force of chondral extracellular matrix, creating a tissue with 65% to 80% water content, their quantitative analysis is important in demonstrating normal functioning of this dynamic tissue.3 The reduction of proteoglycan density in degenerative cartilage is evidence of its importance.4,5 In light of this it is surprising that this study demonstrated no significant difference between cartilage genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) and the controls at four and nine months.

4. In a study of a tissue that is relatively hypocellular, quantitative analysis of the products of chondrocyte metabolism, such as collagen II and matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinase (TIMPs), is very sensitive to differences in chondrocyte density. Was chondrocyte density of the defects quantified, for example using a fluorometric assay with a bisbenzimidazole dye (Hoechst 33258)?6

BA ROGERS, MA, MSc, MRCGP, MRCS,
Specialist Registrar,
NJ LITTLE MSc, MRCS,
Specialist Registrar,
The Princess Royal Hospital,
Haywards Heath, UK.

1. Athanasiou KA, Rosenwasser MP, Buckwalter JA, Malinin TI, Mow VC. Interspecies comparisons of in situ intrinsic mechanical properties of distal femoral cartilage. J Orthop Res 1991;9:330-40.
2. Mow VC, Flatow EL, Ateshian GA. Biomechanics. In: Buckwater JA, Einhorn TA, Simon SR, eds., Orthopaedic Basic Science:Biology and Biomechanics of the Musculoskeletal System. Second ed. Rosemont: American Academy of Orthopaedic Surgeons, 2000:134-80.
3. Mankin HJ, Mow VC, Buckwalter JA, Iannotti JP, Ratcliffe A. Articular Cartilage Structure, Composition and Function. In: Buckwalter JA, Einhorn TA, Simon SR, eds., Orthopaedic Basic Science:Biology and Biomechanics of the Musculoskeletal System. Second ed. Rosemont: American Academy of Orthopaedic Surgeons, 2000:446-70.
4. Bjelle A. Content and composition of glycosaminoglycans in human knee joint cartilage. Variation with site and age in adults. Connect Tissue Res 1975;3:141-7.
5. Ficat C, Maroudas A. Cartilage of the patella. Topographical variation of glycosaminoglycan content in normal and fibrillated tissue. Ann Rheum Dis 1975;34:515-9.
6. Kim YJ, Sah RL, Doong JY, Grodzinsky AJ. Fluorometric assay of DNA in cartilage explants using Hoechst 33258. Anal Biochem 1988;174:168-76.

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