Osteoprotegerin Deficiency Results in Disruption of Posterofrontal Suture Closure in Mice

Beederman, Maureen; Kim, Stephanie H.; Rogers, MJ; Lyon, Sarah; He, Tong‐Chuan; Reid, Russell R.

doi:10.1097/prs.0000000000001284

Cited by 4 publications

(5 citation statements)

References 20 publications

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“… 12 In mice, the posterior frontal suture typically fuses around three weeks after birth, but it exhibits persistent patency in mice lacking osteoprotegerin (OPG), which inhibits osteoclastogenesis by antagonising receptor activator of nuclear factor kappa-B ligand (RANKL). 13 Moreover, downregulation of another osteoclast regulator, receptor activator of nuclear factor kappa-B (RANK), also results in increased bone formation at the suture. 14 …”

Section: Introductionmentioning

confidence: 99%

BMP-IHH-mediated interplay between mesenchymal stem cells and osteoclasts supports calvarial bone homeostasis and repair

Guo

Yuan

Wu³

et al. 2018

Bone Res

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Calvarial bones are connected by fibrous sutures. These sutures provide a niche environment that includes mesenchymal stem cells (MSCs), osteoblasts, and osteoclasts, which help maintain calvarial bone homeostasis and repair. Abnormal function of osteogenic cells or diminished MSCs within the cranial suture can lead to skull defects, such as craniosynostosis. Despite the important function of each of these cell types within the cranial suture, we have limited knowledge about the role that crosstalk between them may play in regulating calvarial bone homeostasis and injury repair. Here we show that suture MSCs give rise to osteoprogenitors that show active bone morphogenetic protein (BMP) signalling and depend on BMP-mediated Indian hedgehog (IHH) signalling to balance osteogenesis and osteoclastogenesis activity. IHH signalling and receptor activator of nuclear factor kappa-Β ligand (RANKL) may function synergistically to promote the differentiation and resorption activity of osteoclasts. Loss of Bmpr1a in MSCs leads to downregulation of hedgehog (Hh) signalling and diminished cranial sutures. Significantly, activation of Hh signalling partially restores suture morphology in Bmpr1a mutant mice, suggesting the functional importance of BMP-mediated Hh signalling in regulating suture tissue homeostasis. Furthermore, there is an increased number of CD200+ cells in Bmpr1a mutant mice, which may also contribute to the inhibited osteoclast activity in the sutures of mutant mice. Finally, suture MSCs require BMP-mediated Hh signalling during the repair of calvarial bone defects after injury. Collectively, our studies reveal the molecular and cellular mechanisms governing cell–cell interactions within the cranial suture that regulate calvarial bone homeostasis and repair.

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Section: Introductionmentioning

confidence: 99%

BMP-IHH-mediated interplay between mesenchymal stem cells and osteoclasts supports calvarial bone homeostasis and repair

Guo

Yuan

Wu³

et al. 2018

Bone Res

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“…However, a reduction or to delay in the suture fusion also plays a key role in shaping the skull. In the case of the OPG KO mouse model, an OPG deficiency created a reduced fusion of the interfrontal suture which was coupled with a shortened skull morphology in the anterior-posterior direction (brachycephaly) ( Beederman et al, 2015 ). Evidence from mouse models suggests that sutures, irrespective of the closure status, can serve as targets for developmental changes that affect the overall cranial morphology.…”

Section: Sutures As Targets For Evolutionary Change In Skull Morphologymentioning

confidence: 99%

“…The patency and osseous obliteration of a suture is largely controlled by the bone remodelling activity of osteoclasts and osteoblasts. A balance between these bone remodelling cells (osteoclasts and osteoblasts) is required for suture homeostasis and the maintenance of a patent suture ( Beederman et al, 2015 ). Given the role of osteoclasts and osteoblasts in determining suture fusion status in mammals, they have a crucial role in regulating the cranial bone growth capacity at the suture.…”

Section: Possible Mechanisms For Evolutionary Changementioning

confidence: 99%

“…FGF signalling is associated with osteoblast differentiation, if disrupted this is one of the critical pathways known to cause premature suture fusion ( Rice et al, 2003 ). Perturbations in the RANK/RANKL/OPG pathway, which is associated with both osteoblast and osteoclast activity, have more recently been linked to alterations in cranial suture fusion, implying that osteoclasts may also play a critical role at the suture locale ( Lee et al, 2011 ; Beederman et al, 2015 ). Osteoclast differentiation and activation through the RANK/RANKL interaction maintains suture patency ( Lee et al, 2011 ).…”

Section: Possible Mechanisms For Evolutionary Changementioning

confidence: 99%

“…Osteoprotegerin (OPG) acts to block this interaction to instead favour osteoblast activity. Therefore, when OPG deficiency occurs, which supports osteoclast differentiation via RANK/RANKL signalling, suture patency is maintained ( Beederman et al, 2015 ). Defects in osteoclast differentiation unsurprisingly are related to premature fusion ( Kawata et al, 1998 ), which have been associated with a downregulation of RANK.…”

Section: Possible Mechanisms For Evolutionary Changementioning

confidence: 99%

See 2 more Smart Citations

The Intertwined Evolution and Development of Sutures and Cranial Morphology

White

Goswami

Tucker

2021

Front. Cell Dev. Biol.

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Phenotypic variation across mammals is extensive and reflects their ecological diversification into a remarkable range of habitats on every continent and in every ocean. The skull performs many functions to enable each species to thrive within its unique ecological niche, from prey acquisition, feeding, sensory capture (supporting vision and hearing) to brain protection. Diversity of skull function is reflected by its complex and highly variable morphology. Cranial morphology can be quantified using geometric morphometric techniques to offer invaluable insights into evolutionary patterns, ecomorphology, development, taxonomy, and phylogenetics. Therefore, the skull is one of the best suited skeletal elements for developmental and evolutionary analyses. In contrast, less attention is dedicated to the fibrous sutural joints separating the cranial bones. Throughout postnatal craniofacial development, sutures function as sites of bone growth, accommodating expansion of a growing brain. As growth frontiers, cranial sutures are actively responsible for the size and shape of the cranial bones, with overall skull shape being altered by changes to both the level and time period of activity of a given cranial suture. In keeping with this, pathological premature closure of sutures postnatally causes profound misshaping of the skull (craniosynostosis). Beyond this crucial role, sutures also function postnatally to provide locomotive shock absorption, allow joint mobility during feeding, and, in later postnatal stages, suture fusion acts to protect the developed brain. All these sutural functions have a clear impact on overall cranial function, development and morphology, and highlight the importance that patterns of suture development have in shaping the diversity of cranial morphology across taxa. Here we focus on the mammalian cranial system and review the intrinsic relationship between suture development and morphology and cranial shape from an evolutionary developmental biology perspective, with a view to understanding the influence of sutures on evolutionary diversity. Future work integrating suture development into a comparative evolutionary framework will be instrumental to understanding how developmental mechanisms shaping sutures ultimately influence evolutionary diversity.

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Whole-Proteome Analysis of Human Craniosynostotic Tissue Suggests a Link between Inflammatory Signaling and Osteoclast Activation in Human Cranial Suture Patency

Lyon

Mayampurath

Song

et al. 2018

Plastic &Amp; Reconstructive Surgery

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Osteoprotegerin Deficiency Results in Disruption of Posterofrontal Suture Closure in Mice

Cited by 4 publications

References 20 publications

BMP-IHH-mediated interplay between mesenchymal stem cells and osteoclasts supports calvarial bone homeostasis and repair

BMP-IHH-mediated interplay between mesenchymal stem cells and osteoclasts supports calvarial bone homeostasis and repair

The Intertwined Evolution and Development of Sutures and Cranial Morphology

Whole-Proteome Analysis of Human Craniosynostotic Tissue Suggests a Link between Inflammatory Signaling and Osteoclast Activation in Human Cranial Suture Patency

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