Application of 3D MAPs pipeline identifies the morphological sequence chondrocytes undergo and the regulatory role of GDF5 in this process

Rubin, Sarah; Agrawal, Ankit; Stegmaier, Johannes; Krief, Sharon; Felsenthal, Neta; Svorai, Jonathan; Addadi, Yoseph; Villoutreix, Paul; Stern, Tomer; Zelzer, Elazar

doi:10.1038/s41467-021-25714-0

Cited by 11 publications

(21 citation statements)

References 96 publications

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“…The advances in elucidating a complete molecular regulatory network will rely on combining imaging, bio information, and genetic models. For example, Rubin et al developed an imaging and analysis pipeline, called 3D Morphometric Analysis for Phenotypic significance (3D MAPs), which creates 3D morphology maps of the growth plate by using a procedure to clear tissue, segment chondrocytes, and project cells onto their locations [ 92 ]. Three-dimensional MAPs revealed continuous morphogenetic behaviors of chondrocytes within the growth plate.…”

Section: Summary and Future Perspectivesmentioning

confidence: 99%

Roles of Local Soluble Factors in Maintaining the Growth Plate: An Update

Zhang

Ahmadpoor

Lin

2023

Genes

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The growth plate is a cartilaginous tissue found at the ends of growing long bones, which contributes to the lengthening of bones during development. This unique structure contains at least three distinctive layers, including resting, proliferative, and hypertrophic chondrocyte zones, maintained by a complex regulatory network. Due to its soft tissue nature, the growth plate is the most susceptible tissue of the growing skeleton to injury in childhood. Although most growth plate damage in fractures can heal, some damage can result in growth arrest or disorder, impairing leg length and resulting in deformity. In this review, we re-visit previously established knowledge about the regulatory network that maintains the growth plate and integrate current research displaying the most recent progress. Next, we highlight local secretary factors, such as Wnt, Indian hedgehog (Ihh), and parathyroid hormone-related peptide (PTHrP), and dissect their roles and interactions in maintaining cell function and phenotype in different zones. Lastly, we discuss future research topics that can further our understanding of this unique tissue. Given the unmet need to engineer the growth plate, we also discuss the potential of creating particular patterns of soluble factors and generating them in vitro.

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Section: Summary and Future Perspectivesmentioning

confidence: 99%

Roles of Local Soluble Factors in Maintaining the Growth Plate: An Update

Zhang

Ahmadpoor

Lin

2023

Genes

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Section: Introductionmentioning

confidence: 99%

“…Over recent years, progress has been made in characterising the cellular dynamics involved in tissue growth. Spatial morphometric analyses were conducted on light-sheet images of the embryonic murine tibia, revealing that a number of cell morphological changes and growth strategies contribute to growth plates’ expansion, especially highly spatially-dependent cell volume expansions [45]. Quantification of tissue growth based on cell lineage tracking data in the developing chick limb bud [46] and the Drosophilia wing disc [47] showed that spatially and temporally heterogeneous growth patterns coupled with growth anisotropy are major drivers of tissue morphogenesis.…”

Section: Introductionmentioning

confidence: 99%

Cyclical compression loading is the dominant mechanoregulator of synovial joint morphogenesis

Godivier¹,

Lawrence²,

Wang³

et al. 2023

Preprint

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Mechanical stimuli arising from fetal movements are critical factors underlying joint growth. Abnormal fetal movements negatively affect joint shape features with important implications for joint function and health, but the mechanisms by which mechanical forces due to fetal movements influence joint growth are still unclear. In this research, we integrated cell-level data into a novel mechanobiological model of zebrafish jaw joint morphogenesis to identify links between the mechanical stimuli arising from movement and patterns of growth. Larval zebrafish jaw joint growth patterns were quantified from tracked cell-data at several successive developmental stages in the presence or absence of movements. Pharmacological immobilisation, prior to the onset of jaw movements, resulted in growth rate decreases which were stronger along the ventrodorsal axis. Simulations of joint morphogenesis, based on quantified cell-level data and which integrated mechanical stimuli arising from simulated jaw movements, were used to test hypotheses relating specific mechanical stimuli with the local changes in size and shape. Different types of mechanical stimulation were incorporated into the simulation to provide the mechanoregulated component on growth in addition to the baseline (non mechanoregulated) growth which occurs in the immobilised animals. We found that the magnitude of compression experienced during joint motion when included as the stimulus for mechanoregulated growth could not predict the real, normally loaded shaped joints. However, when the dynamic changes caused by the application of cyclical compression was implemented as the stimulus for mechanoregulated growth, the sizes and shapes of joints were correctly simulated. We conclude therefore that the cyclical application of compression loading due to the dynamic nature of fetal movements underlies the mechanoregulation of prenatal joint morphogenesis. Our results provide a fundamental advance in our understanding of mechanoregulation of the developing joint and increase our understanding of the origins of conditions such as hip dysplasia and arthrogryposis.

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“…There is a growing body of research quantifying cellular dynamics involved in growth and morphogenesis using computational tools. Rubin et al (2021) Suzuki & Morishita, 2017;Tozluoglu et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…There is a growing body of research quantifying cellular dynamics involved in growth and morphogenesis using computational tools. Rubin et al ( 2021 ) built 3D maps of cell morphologies from light‐sheet images of the embryonic murine tibia. Cell density, surface area, volume and orientation were quantified and spatially analysed revealing that differential cell volume expansion underlies tissue morphogenesis of the developing growth plates.…”

Section: Introductionmentioning

confidence: 99%