Articular-cartilage proteoglycans in aging and osteoarthritis

Inerot, Sven; Heinegård, Dick; Audell, Lars; Olsson, Sten‐Erik

doi:10.1042/bj1690143

Cited by 222 publications

(63 citation statements)

References 31 publications

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“…Articular cartilage is a multiphasic tissue, the solid phase of which is composed predominately of a collagen (mainly type II) fibrillar network (around 10-22% by wet weight) enmeshing proteoglycan macromolecules (2-7% by wet weight) (Maroudas et al, 1969;Muir et al, 1970;Bayliss and Ali, 1978;Inerot et al, 1978;Maroudas et al, 1980;Zirn et al, 1984;Mow et al, 1992;Rieppo et al, 2009;Gannon et al, 2012). Previous studies have demonstrated that the application of dynamic compression (Huang et al, 2010;Bian et al, 2012;Thorpe et al, 2013) or hydrostatic pressure (Miyanishi et al, 2006;Wagner et al, 2008;Ogawa et al, 2009;Huang et al, 2010;Meyer et al, 2011;Correia et al, 2012;Liu et al, 2012;Steward et al, 2012;Vinardell et al, 2012a;Liu et al, 2013) can enhance the sGAG and collagen content as well as the mechanical functionality of cartilage constructs engineered using MSCs.…”

Section: Discussionmentioning

confidence: 99%

Cyclic hydrostatic pressure promotes a stable cartilage phenotype and enhances the functional development of cartilaginous grafts engineered using multipotent stromal cells isolated from bone marrow and infrapatellar fat pad

Carroll

Buckley

Kelly

2014

Journal of Biomechanics

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a b s t r a c tThe objective of this study was to investigate how joint specific biomechanical loading influences the functional development and phenotypic stability of cartilage grafts engineered in vitro using stem/progenitor cells isolated from different source tissues. Porcine bone marrow derived multipotent stromal cells (BMSCs) and infrapatellar fat pad derived multipotent stromal cells (FPSCs) were seeded in agarose hydrogels and cultured in chondrogenic medium, while simultaneously subjected to 10 MPa of cyclic hydrostatic pressure (HP). To mimic the endochondral phenotype observed in vivo with cartilaginous tissues engineered using BMSCs, the culture media was additionally supplemented with hypertrophic factors, while the loss of phenotype observed in vivo with FPSCs was induced by withdrawing transforming growth factor (TGF)-β3 from the media. The application of HP was found to enhance the functional development of cartilaginous tissues engineered using both BMSCs and FPSCs. In addition, HP was found to suppress calcification of tissues engineered using BMSCs cultured in chondrogenic conditions and acted to maintain a chondrogenic phenotype in cartilaginous grafts engineered using FPSCs. The results of this study point to the importance of in vivo specific mechanical cues for determining the terminal phenotype of chondrogenically primed multipotent stromal cells. Furthermore, demonstrating that stem or progenitor cells will appropriately differentiate in response to such biophysical cues might also be considered as an additional functional assay for evaluating their therapeutic potential.

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Section: Discussionmentioning

confidence: 99%

Cyclic hydrostatic pressure promotes a stable cartilage phenotype and enhances the functional development of cartilaginous grafts engineered using multipotent stromal cells isolated from bone marrow and infrapatellar fat pad

Carroll

Buckley

Kelly

2014

Journal of Biomechanics

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“…Accompanying this loss is an increase in water content, as well as disturbances in the chemistry of the remaining proteoglycans (1,(6)(7)(8)(9)(10) In the present study we have measured the activity of neutral proteases in human OA cartilage by their action on endogenous proteoglycans using a micromethod modified from the procedure of Sapolsky et a1 (15). We havc demonstrated a significant elevation of neutral metalloprotease activity in OA specimens, particularly in the modcrate-severe stages of the disease.…”

mentioning

confidence: 99%

“…Accompanying this loss is an increase in water content, as well as disturbances in the chemistry of the remaining proteoglycans (1,(6)(7)(8)(9)(10). These proteoglycans show greater extractibility, smaller hydrodynamic size, and partial loss of their ability to aggregate.…”

mentioning

confidence: 99%

Neutral proteases capable of proteoglycan digesting activity in osteoarthritic and normal human articular cartilage

Martel‐Pelletier¹,

Pelletier²,

Cloutier³

et al. 1984

Arthritis & Rheumatism

155

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Proteases have been postulated to account for the progressive disappearance of matrix proteoglycans in osteoarthritic (OA) cartilage. The digestion of endogenous proteoglycans by neutral proteases in human OA cartilage homogenates has been measured and compared with that of normal age-matched controls. Cartilage was obtained from 16 patients at the time of knee arthroplasty and from 7 accident victims. Tissue blocks were cut from the tibia1 plateau; part was used for histologic grading of the severity of OA and part was homogenized for the quantification of neutral metalloand serine protease activities, based on the release of digested products from endogenous proteoglycans. Total metalloprotease activity (latent plus active forms) was elevated 3-to 10-fold in all diseased cartilage. This elevation was already significant in mild disease, but was greatest in samples of moderate to severe disease. The active form of the enzyme was highest at the center of erosions and decreased in the margins of the plateau. The digestion of proteoglycans, as distinct from their mere release from the tissue, was demonstrated by chromatography on Sepharose-CL2B and by large pore electrophoresis. Serine protease activity on proteoglycans was much lower than that of metalloprotease. The mean activity was highest in mild disease and declined in the severe disease samples, but the difference between these 2 groups and the controls was not statistically significant. The results of this study are consistent with the hypothesis that the neutral metalloproteases of cartilage are involved in the degradation of proteoglycans in osteoarthritis.Although the etiologic mechanisms of osteoarthritis remain unknown, one fundamental finding is always the progressive degeneration and erosion of articular cartilage. In early stages of the disease there is a consistent loss of matrix proteoglycans, as evaluated by histochemical and biochemical means (1-5).Accompanying this loss is an increase in water content, as well as disturbances in the chemistry of the remaining proteoglycans (1,(6)(7)(8)(9)(10) In the present study we have measured the activity of neutral proteases in human OA cartilage by their action on endogenous proteoglycans using a micromethod modified from the procedure of Sapolsky et a1 (15). We havc demonstrated a significant elevation of neutral metalloprotease activity in OA specimens, particularly in the modcrate-severe stages of the disease. A second protease activity of the serine type appeared to be quantitatively less important. Serine activity tended to rise in OA, but the elevation was not statistically significant. MATERIALS AND METHODS Chemicals. The chemicals used were either AmericanChemical Society certified or the best grade commercially available. DNA calf thymus type I, chondroitin sulfate, and phenylmethylsulfonyl fluoride (PMS-F) were purchased from Sigma Chemical Co., St. Louis, MO; bovine trypsin inhibitor from Boehringer Mannheim, Indianapolis, IN; paminophenylmercuric acetate (APMA), cetylpyridinium chloride, and ...

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“…Decrease in size of the proteoglycan monomers and chondroitin sulfate chains with age has been reported before (25)(26)(27)(28). The very large exclusion limit of Fractogel HW-75S, however, makes it possible to show that the size of proteoglycan aggregates also decreases with age.…”

Section: Discussionmentioning

confidence: 87%

Heterogeneity of proteoglycans extracted before and after collagenase treatment of human articular cartilage: I. Physical properties related to age

Stadt¹,

Kuijer²,

Kampen³

et al. 1986

Arthritis & Rheumatism

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Proteoglycans were isolated from young and mature human articular cartilage 4 different ways: by direct extraction with 4M guanidine hydrochloride (GuHC1); after digestion of the residue from this first extraction with collagenase, by extraction with 4M GuHCI; associatively with 0.5M GuHCl after digestion of the cartilage with collagenase; and dissociatively with 4M GuHCl after digestion of the cartilage with collagenase. The structural properties of these proteoglycans were compared. Proteoglycan aggregates and monomers isolated from second extractions and from young cartilage were of larger hydrodynamic size than proteoglycans isolated from first extractions and mature Cartilage, respectively. The same applied to the chondroitin sulfate chain lengths of these proteoglycans. The proteoglycan fraction from second extractions of Cartilage contained a larger proportion of monomers than the fraction from first extractions. Associative extraction of mature collagenase-digested cartilage yielded mainly proteoglycan monomers, whereas an appreciable amount of proteoglycan aggregate was also liberated from young collagenase-digested cartilage. proteoglycans from second extractions of cartilage are more entrapped in the collagen network. These large proteoglycans can only be liberated from the matrix after extraction of the smaller proteoglycans, followed by digestion of the residue with collagenase. This indicates that proteoglycans overlap and entangle with the collagen and protect it from degradation by collagenase.

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Articular-cartilage proteoglycans in aging and osteoarthritis

Cited by 222 publications

References 31 publications

Cyclic hydrostatic pressure promotes a stable cartilage phenotype and enhances the functional development of cartilaginous grafts engineered using multipotent stromal cells isolated from bone marrow and infrapatellar fat pad

Cyclic hydrostatic pressure promotes a stable cartilage phenotype and enhances the functional development of cartilaginous grafts engineered using multipotent stromal cells isolated from bone marrow and infrapatellar fat pad

Neutral proteases capable of proteoglycan digesting activity in osteoarthritic and normal human articular cartilage

Heterogeneity of proteoglycans extracted before and after collagenase treatment of human articular cartilage: I. Physical properties related to age

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