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The life cycle of chondrocytes in the developing skeleton.

ABSTRACT: Cartilage serves multiple functions in the developing embryo and in postnatal life. Genetic mutations affecting cartilage development are relatively common and lead to skeletal malformations, dysfunction or increased susceptibility to disease or injury. Characterization of these mutations and investigation of the molecular pathways in which these genes function have contributed to an understanding of the mechanisms regulating skeletal patterning, chondrogenesis, endochondral ossification and joint formation. Extracellular growth and differentiation factors including bone morphogenetic proteins, fibroblast growth factors, parathyroid hormone-related peptide, extracellular matrix components, and members of the hedgehog and Wnt families provide important signals for the regulation of cell proliferation, differentiation and apoptosis. Transduction of these signals within the developing mesenchymal cells and chondrocytes results in changes in gene expression mediated by transcription factors including Smads, Msx2, Sox9, signal transducer and activator of transcription (STAT), and core-binding factor alpha 1. Further investigation of the interactions of these signaling pathways will contribute to an understanding of cartilage growth and development, and will allow for the development of strategies for the early detection, prevention and treatment of diseases and disorders affecting the skeleton.

SUBMITTER: Shum L

PROVIDER: S-EPMC128921 | biostudies-literature | 2002

REPOSITORIES: biostudies-literature

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The life cycle of chondrocytes in the developing skeleton.

Shum Lillian L Nuckolls Glen G

Arthritis research 20011108 2

Cartilage serves multiple functions in the developing embryo and in postnatal life. Genetic mutations affecting cartilage development are relatively common and lead to skeletal malformations, dysfunction or increased susceptibility to disease or injury. Characterization of these mutations and investigation of the molecular pathways in which these genes function have contributed to an understanding of the mechanisms regulating skeletal patterning, chondrogenesis, endochondral ossification and joi ...[more]

PMID: 11879545

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Project description:We previously found that FoxA factors are necessary for chondrocyte differentiation. To investigate whether FoxA factors alone are sufficient to drive chondrocyte hypertrophy, we build a FoxA2 transgenic mouse in which FoxA2 cDNA is driven by a reiterated Tetracycline Response Element (TRE) and a minimal CMV promoter. This transgenic line was crossed with a col2CRE;Rosa26rtTA/+ mouse line to generate col2CRE;Rosa26rtTA/+;TgFoxA2+/- mice for inducible expression of FoxA2 in cartilage using doxycycline treatment. Ectopic expression of FoxA2 in the developing skeleton reveals skeletal defects and shorter skeletal elements in E17.5 mice. The chondro-osseous border was frequently mis-shaped in mutant mice, with small islands of col.10+ hypertrophic cells extending in the metaphyseal bone. Even though overexpression of FoxA2 causes an accumulation of hypertrophic chondrocytes, it did not trigger ectopic hypertrophy in the immature chondrocytes. This suggests that FoxA2 may need transcriptional co-factors (such as Runx2), whose expression is restricted to the hypertrophic zone, and absent in the immature chondrocytes. To investigate a potential FoxA2/Runx2 interaction in immature chondrocytes versus hypertrophic cells, we separated these two subpopulations by FACS to obtain CD24+CD200+ hypertrophic chondrocytes and CD24+CD200- immature chondrocytes and we ectopically expressed FoxA2 alone or in combination with Runx2 via lentiviral gene delivery. In CD24+CD200+ hypertrophic chondrocytes, FoxA2 enhanced the expression of chondrocyte hypertrophic markers collagen 10, MMP13, and alkaline phosphatase. In contrast, in the CD24+CD200- immature chondrocytes, neither FoxA2 nor Runx2 overexpression could induce ectopic expression of hypertrophic markers MMP13, alkaline phosphatase, or PTH/PTHrP receptor. Overall these findings mirror our in vivo data, and suggest that induction of chondrocyte hypertrophy by FoxA2 may require other factors in addition to Runx2 (i.e., Hif2α, MEF2C, or perhaps unknown factors), whose expression/activity is rate-limiting in immature chondrocytes.

Project description:BackgroundQuantitative studies of the variation of disparity during ontogeny exhibited by the radiation of coral reef fishes are lacking. Such studies dealing with the variation of disparity, i.e. the diversity of organic form, over ontogeny could be a first step in detecting evolutionary mechanisms in these fishes. The damselfishes (Pomacentridae) have a bipartite life-cycle, as do the majority of demersal coral reef fishes. During their pelagic dispersion phase, all larvae feed on planktonic prey. On the other hand, juveniles and adults associated with the coral reef environment show a higher diversity of diets. Using geometric morphometrics, we study the ontogenetic dynamic of shape disparity of different head skeletal units (neurocranium, suspensorium and opercle, mandible and premaxilla) in this fish family. We expected that larvae of different species might be relatively similar in shapes. Alternatively, specialization may become notable even in the juvenile and adult phase.ResultsThe disparity levels increase significantly throughout ontogeny for each skeletal unit. At settlement, all larval shapes are already species-specific. Damselfishes show high levels of ontogenetic allometry during their post-settlement growth. The divergence of allometric patterns largely explains the changes in patterns and levels of shape disparity over ontogeny. The rate of shape change and the length of ontogenetic trajectories seem to be less variable among species. We also show that the high levels of shape disparity at the adult stage are correlated to a higher level of ecological and functional diversity in this stage.ConclusionDiversification throughout ontogeny of damselfishes results from the interaction among several developmental novelties enhancing disparity. The bipartite life-cycle of damselfishes exemplifies a case where the variation of environmental factors, i.e. the transition from the more homogeneous oceanic environment to the coral reef offering a wide range of feeding habits, promotes increasing shape disparity of the head skeleton over the ontogeny of fishes.

Project description:Municipal Solid Waste (MSW) management has been a long-standing problem for many cities in developing countries. Urbanization, population growth, and excessive demand for resources caused significant waste related environmental and socio-economic problems in cities. Integration of policy decisions with actionable targets and management of economic and environmental extremes were common challenges to achieving sustainable waste management strategy. Circular economy is a concept that has been evolved with sustainable resource management perspective adopted in this study to support scientific decision-making process for urban planners and policymakers. Life Cycle Assessment (LCA) is a framework to assess the environmental impacts of waste life cycle ranging from waste generation, transportation, treatment, and end disposal. This study used the LCA framework to evaluate the impact of MSW management of a selected local authority in Colombo, Sri Lanka, to identify the environmental impact of four (04) proposed scenarios in comparison with the Business-As-Usual (BAU) scenario. Environmental impacts were calculated using global warming potential in terms of greenhouse gas emissions and short-lived climate pollutants. The results revealed that management of MSW within the local authority boundary by integrating recycling, incineration, and sanitary landfill (3:8:1 ratio) offered the highest positive impacts (- 121.84 kg of CO2 eq./ton) while BAU scenario caused the highest negative impacts (250.97 kg of CO2 eq./ton) in comparison with selected scenarios. Moreover, incineration, sanitary landfill, recycling, and anaerobic digestion contributed to emission savings and energy generation. LCA framework was used to identify the composition of MSW for suitable technologies as well as to evaluate the efficiency of existing management mechanisms within a local authority. Evaluation was used to understand the holistic picture of multiple management options to support policymakers in the decision-making process. This framework can be used as a benchmarking tool and bridging concept between the waste management policy and local action plans, which is an important step towards achieving a circular economy for developing countries.Supplementary informationThe online version contains supplementary material available at 10.1007/s43615-022-00200-x.

Dataset Information

The life cycle of chondrocytes in the developing skeleton.

Publications

The life cycle of chondrocytes in the developing skeleton.

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