Elevated extracellular calcium concentrations induce type X collagen synthesis in chondrocyte cultures.

Bonen, Denise K.; Schmid, Thomas

doi:10.1083/jcb.115.4.1171

Cited by 82 publications

(50 citation statements)

References 58 publications

(52 reference statements)

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“…Collagen production was reported to be the lowest at [Ca 2+ ] = 1 to 2mM in a chondrocyte-monolayer study, and an increase of [Ca 2+ ] from 2mM stimulated collagen production [12]. Other studies show that a lower calcium level can stimulate the Type X collagen synthesis and suppress the Type I collagen synthesis while leaving the Type II collagen unchanged [46,47]. No significant effect of calcium concentration on GAG production has been reported.…”

Section: Discussionmentioning

confidence: 96%

Calcium Concentration Effects on the Mechanical and Biochemical Properties of Chondrocyte-Alginate Constructs

et al. 2008

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Alginate gel crosslinked by calcium ions (Ca 2+ ) has been widely used in cartilage tissue engineering. However, most studies have been largely performed in vitro in medium with a calcium concentration ([Ca 2+ ]) of 1.8mM, while the calcium level in the synovial fluid of the human knee joints, for example, has been reported to be 4mM or even higher. To simulate the synovial environment, the two studies in this paper were designed to investigate how the alginate scaffold alone, as well as the chondrocytes seeded alginate gel responds to variations in medium [Ca 2+ ]. In Study A, the mechanical properties of 2% alginate hydrogel were tested in 0.15M NaCl and various [Ca 2+ ] (1.0mM, 1.8mM, and 4mM). In Study B, primary bovine chondrocytes was seeded in alginate gel, and biochemical contents and mechanical properties were determined after incubation for 28 days in three [Ca 2+ ] (1.8mM, 4mM, and 8mM). For both studies, it was found that the magnitude of the complex shear modulus (|G*|) at 1Hz doubled and the corresponding phase angle shift angle (δ) increased > 2° as a result of the approximate 4-fold change in [Ca 2+ ]. At high [Ca 2+ ], the chondrocyte glycosaminogylcan (GAG) production inside the chondrocyte-alginate constructs was suppressed significantly. This is likely due to a decrease in the porosity of the chondrocyte-alginate constructs as a result of compaction in structure caused by an increased crosslinking density with [Ca 2+ ]. These may be important considerations in the eventual successful implementation of cartilage tissueengineered constructs in the clinical setting.

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Section: Discussionmentioning

confidence: 96%

Calcium Concentration Effects on the Mechanical and Biochemical Properties of Chondrocyte-Alginate Constructs

et al. 2008

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“…Of particular interest here is the work of Deshmukh and colleagues (Deshmukh et al, 1976, which demonstrates that isolated chondrocytes, when maintained in suspension culture, produce primarily type I1 collagen in medium lacking CaCl,, and type I collagen in complete medium. Mature chondrocytes isolated from sternal hyaline cartilage also express type X collagen when cultured in excess medium calcium (Bonen and Schmid, 1991). Additionally, several studies concluded that a critical concentration of intracellular calcium is necessary for normal synthesis of skeletal extracellular matrix and Chojkier, 1986).…”

Section: Discussionmentioning

confidence: 99%

Chondrogenic potential of chick embryonic calvaria: II. Matrix calcium may repress cartilage differentiation

Jacenko

Antonio

Tuan

1995

Developmental Dynamics

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Chick embryos cultured in the absence of their eggshell are rendered severely calcium-deficient, and develop a cartilage-like phenotype in the calvarium, a normally osteogenic tissue. In the preceding paper (Jacenko and Tuan [1995] Dev. Dyn. 20213-26), experiments using organ cultured calvaria from day-12 normal and shell-less embryos showed that depletion of calcium alone may be responsible in promoting chondrogenic differentiation in calvaria. Here these findings were extended using an in vivo calvarial grafting technique, such that the extent of calvarial matrix calcification was a function of the calcium status of both the graft and the host. In these calvarial grafts, undermineralized regions again were shown to support chondrogenesis. To identify possible mechanisms which promote chondrogenesis in the calvaria, cells were enzymatically dissociated from the calvaria and cultured in media with varied levels of soluble calcium, under conditions which should modulate cell-to-cell interactions, including monolayer, micromass, agarose gels, and suspension cultures. Soluble calcium had no effect on calvarial cell differentiation, whereas conditions which enhanced cell-cell interactions, e.g., suspension culture, elicited cartilage expression. Based on these findings, we propose that the calcified matrix of the calvarium is repressive to chondrogenesis during normal development, but that the lack of mineral in a calcium-deficient calvarium creates a microenvironment permissive for cell-to-cell interactions which lead to chondrogenic differentiation. 0 1995 Wiley-Liss, Inc.

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“…Whether this inhibition occurs at the level of transcription, translation, or secretion is under investigation. In the presence of elevated concentrations of extracellular calcium, type X collagen synthesis is increased dramatically while type I1 collagen synthesis is not increased (39). Chondrocytes are sensitive to changes in intracellular calcium concentrations, beginning with their initial differentiation from mesenchyma (40).…”

Section: Discussionmentioning

confidence: 99%

Doxycycline disrupts chondrocyte differentiation and inhibits cartilage matrix degradation

Cole

Chubinskaya

Luchene

et al. 1994

Arthritis & Rheumatism

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Objective. The effects of doxycycline were tested in an in vitro system in which the cartilages of embryonic avian tibias are completely degraded.Methods. Tibias were cultured with 5, 20, or 40 pg/ml doxycycline. Control tibias were cultured without doxycycline. Conditioned media and tissue sections were examined for enzyme activity and matrix loss.Results. Cartilages were not resorbed in the presence of doxycycline, whereas control cartilages were completely degraded. Collagen degradation was reduced in association with treatment with doxycycline at all doses studied. Higher concentrations of doxycycline reduced collagenase and gelatinase activity and prevented proteoglycan loss, cell death, and deposition of type X collagen in the cartilage matrix; in addition, treatment with doxycycline at higher concentrations caused increases in the length of the hypertrophic region.Conclusion. The effects of doxycycline extend beyond inhibition of the proteolytic enzymes by stimulating cartilage growth and disrupting the terminal differentiation of chondrocytes.

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Elevated extracellular calcium concentrations induce type X collagen synthesis in chondrocyte cultures.

Cited by 82 publications

References 58 publications

Calcium Concentration Effects on the Mechanical and Biochemical Properties of Chondrocyte-Alginate Constructs

Calcium Concentration Effects on the Mechanical and Biochemical Properties of Chondrocyte-Alginate Constructs

Chondrogenic potential of chick embryonic calvaria: II. Matrix calcium may repress cartilage differentiation

Doxycycline disrupts chondrocyte differentiation and inhibits cartilage matrix degradation

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