Cranial Base Synchondrosis: Chondrocytes at the Hub

Hallett, Shawn A; Ono, Wanida; Franceschi, Renny T.; Ono, Noriaki

doi:10.3390/ijms23147817

Cited by 12 publications

(18 citation statements)

References 150 publications

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“…Skull elongation is mainly driven by endochondral ossification at the cranial base ( Hallett et al, 2022 ). The impaired AP skull growth observed in Ddr2 slie/slie mice prompt us to examine the cranial base synchondroses and associated bones.…”

Section: Resultsmentioning

confidence: 99%

Control of craniofacial development by the collagen receptor, discoidin domain receptor 2

Mohamed

Hallett

et al. 2023

eLife

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Development of the craniofacial skeleton requires interactions between progenitor cells and the collagen-rich extracellular matrix (ECM). The mediators of these interactions are not well-defined. Mutations in the discoidin domain receptor 2 gene (DDR2), which encodes a non-integrin collagen receptor, are associated with human craniofacial abnormalities, such as midface hypoplasia and open fontanels. However, the exact role of this gene in craniofacial morphogenesis is not known. As will be shown, Ddr2-deficient mice exhibit defects in craniofacial bones including impaired calvarial growth and frontal suture formation, cranial base hypoplasia due to aberrant chondrogenesis and delayed ossification at growth plate synchondroses. These defects were associated with abnormal collagen fibril organization, chondrocyte proliferation and polarization. As established by localization and lineage tracing studies, Ddr2 is expressed in progenitor cell-enriched craniofacial regions including sutures and synchondrosis resting zone cartilage, overlapping with GLI1+ cells, and contributing to chondrogenic and osteogenic lineages during skull growth. Tissue-specific knockouts further established the requirement for Ddr2 in GLI+ skeletal progenitors and chondrocytes. These studies establish a cellular basis for regulation of craniofacial morphogenesis by this understudied collagen receptor and suggest that DDR2 is necessary for proper collagen organization, chondrocyte proliferation and orientation.

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Section: Resultsmentioning

confidence: 99%

Control of craniofacial development by the collagen receptor, discoidin domain receptor 2

Mohamed

Hallett

et al. 2023

eLife

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“… 9 During development growth plates (synchondroses) separate the sphenoid, ethmoidal and basioccipital bones at the base of the skull. 44 Presumably, disturbances in metaphyseal bone modeling similar to those observed in limbs is responsible for cranial base sclerosis observed in Pyle’s disease subjects. Skull shape appears normal as SFRP4 does not affect longitudinal growth.…”

Section: Discussionmentioning

confidence: 99%

Skeletal phenotypes in secreted frizzled-related protein 4 gene knockout mice mimic skeletal architectural abnormalities in subjects with Pyle’s disease from SFRP4 mutations

2023

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Mutations in SFRP4 cause Pyle’s bone disease with wide metaphyses and increased skeletal fragility. The WNT signaling pathway plays important roles in determining skeletal architecture and SFRP4 is a secreted Frizzled decoy receptor that inhibits WNT signaling. Seven cohorts of male and female Sfrp4 gene knockout mice, examined through 2 years of age, had a normal lifespan but showed cortical and trabecular bone phenotypes. Mimicking human Erlenmeyer flask deformities, bone cross-sectional areas were elevated 2-fold in the distal femur and proximal tibia but only 30% in femur and tibia shafts. Reduced cortical bone thickness was observed in the vertebral body, midshaft femur and distal tibia. Elevated trabecular bone mass and numbers were observed in the vertebral body, distal femur metaphysis and proximal tibia metaphysis. Midshaft femurs retained extensive trabecular bone through 2 years of age. Vertebral bodies had increased compressive strength, but femur shafts had reduced bending strength. Trabecular, but not cortical, bone parameters in heterozygous Sfrp4 mice were modestly affected. Ovariectomy resulted in similar declines in both cortical and trabecular bone mass in wild-type and Sfrp4 KO mice. SFRP4 is critical for metaphyseal bone modeling involved in determining bone width. Sfrp4 KO mice show similar skeletal architecture and bone fragility deficits observed in patients with Pyle’s disease with SFRP4 mutations.

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“…The growth and development of the cranial base are incompletely understood [ 11 , 12 , 13 , 14 ], unlike those of the long bone that have been thoroughly studied [ 15 , 16 ]. Developmentally, the SOS is derived from both the mesoderm and the neural crest, whereas the ISS is solely derived from the neural crest [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Given their genetic similarity to humans, we utilize several transgenic mouse models in this study to discern the regulation of the cranial base synchondroses. The growth and development of the cranial base are incompletely understood [11][12][13][14], unlike those of the long bone that have been thoroughly studied [15,16]. Developmentally, the SOS is derived from both the mesoderm and the neural crest, whereas the ISS is solely derived from the neural crest [3].…”

Section: Introductionmentioning

confidence: 99%

“…IHH also enhances PTHrP expression in the round chondrocyte layer [20]. Mice lacking PTHrP display reduced proliferation of chondrocytes associated with premature hypertrophy and accelerated bone The growth and development of the cranial base are incompletely understood [11][12][13][14], unlike those of the long bone that have been thoroughly studied [15,16]. Developmentally, the SOS is derived from both the mesoderm and the neural crest, whereas the ISS is solely derived from the neural crest [3].…”

Section: Introductionmentioning

confidence: 99%

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Cranial Base Synchondrosis Lacks PTHrP-Expressing Column-Forming Chondrocytes

Hallett

Zhou

Herzog

et al. 2022

IJMS

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The cranial base contains a special type of growth plate termed the synchondrosis, which functions as the growth center of the skull. The synchondrosis is composed of bidirectional opposite-facing layers of resting, proliferating, and hypertrophic chondrocytes, and lacks the secondary ossification center. In long bones, the resting zone of the epiphyseal growth plate houses a population of parathyroid hormone-related protein (PTHrP)-expressing chondrocytes that contribute to the formation of columnar chondrocytes. Whether PTHrP+ chondrocytes in the synchondrosis possess similar functions remains undefined. Using Pthrp-mCherry knock-in mice, we found that PTHrP+ chondrocytes predominantly occupied the lateral wedge-shaped area of the synchondrosis, unlike those in the femoral growth plate that reside in the resting zone within the epiphysis. In vivo cell-lineage analyses using a tamoxifen-inducible Pthrp-creER line revealed that PTHrP+ chondrocytes failed to establish columnar chondrocytes in the synchondrosis. Therefore, PTHrP+ chondrocytes in the synchondrosis do not possess column-forming capabilities, unlike those in the resting zone of the long bone growth plate. These findings support the importance of the secondary ossification center within the long bone epiphysis in establishing the stem cell niche for PTHrP+ chondrocytes, the absence of which may explain the lack of column-forming capabilities of PTHrP+ chondrocytes in the cranial base synchondrosis.

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Cranial Base Synchondrosis: Chondrocytes at the Hub

Cited by 12 publications

References 150 publications

Control of craniofacial development by the collagen receptor, discoidin domain receptor 2

Control of craniofacial development by the collagen receptor, discoidin domain receptor 2

Skeletal phenotypes in secreted frizzled-related protein 4 gene knockout mice mimic skeletal architectural abnormalities in subjects with Pyle’s disease from SFRP4 mutations

Cranial Base Synchondrosis Lacks PTHrP-Expressing Column-Forming Chondrocytes

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