Growth of cranial synchondroses and sutures requires polycystin-1

Kolpakova-Hart, Elona; McBratney-Owen, Brandeis; Hou, Bo; Fukai, Naomi; Nicolae, Claudia M.; Zhou, Jing; Olsen, Bjørn R.

doi:10.1016/j.ydbio.2008.07.005

Cited by 41 publications

(57 citation statements)

References 48 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…17 In our study, the hypoplastic maxilla and the subsequent skeletal Class III could be associated with the palatal tipping of the upper incisors we observed in the mutant mice. Based on the analysis of the skull phenotype observed in Pkd1-deficient mice, Kolpakova-Hart et al 17 hypothesized that tensile force within the growing viscerocranium is essential for skeletal growth and that PC1 is an important mediator of this process, as it controls proliferation of mesenchymal cells at the osteogenic fronts. Later on, Hou et al 18 demonstrated that these mutant mice exhibited an impaired response to tensile force.…”

Section: Discussionsupporting

confidence: 54%

See 1 more Smart Citation

Role of polycystin-1 in bone remodeling:Orthodontic tooth movement study in mutant mice

Shalish

Will

Fukai

et al. 2014

The Angle Orthodontist

Self Cite

View full text Add to dashboard Cite

Objective: To test the hypothesis that polycystin-1 (PC1) is involved in orthodontic tooth movement as a mechanical sensor. Materials and Methods: The response to force application was compared between three mutant and four wild-type 7-week-old mice. The mutant mice were PC1/Wnt1-cre, lacking PC1 in the craniofacial region. An orthodontic closed coil spring was bonded between the incisor and the left first molar, applying 20 g of force for 4 days. Micro-computed tomography, hematoxylin and eosin staining, and tartrate-resistent acid phosphatase (TRAP) staining were used to study the differences in tooth movement among the groups. Results: In the wild-type mice the bonded molar moved mesially, and the periodontal ligament (PDL) was compressed in the compression side. The compression side showed a hyalinized zone, and osteoclasts were identified there using TRAP staining. In the mutant mice, the molar did not move, the incisor tipped palatally, and there was slight widening of the PDL in the tension area. Osteoclasts were not seen on the bone surface or on the compression side. Osteoclasts were only observed on the other side of the bone-in the bone marrow. Conclusions: These results suggest a difference in tooth movement and osteoclast activity between PC1 mutant mice and wild-type mice in response to orthodontic force. The impaired tooth movement and the lack of osteoclasts on the bone surface in the mutant working side may be related to lack of signal from the PDL due to PC1 deficiency. (Angle Orthod. 2014;84:885-890.)

show abstract

Section: Discussionsupporting

confidence: 54%

“…Current studies [15][16][17][18][19] specific to the effect of primary cilia on skeletal growth and mechanical stress indeed showed promising results in support of the PC1 sensor role hypothesis.…”

Section: Introductionmentioning

confidence: 83%

Role of polycystin-1 in bone remodeling:Orthodontic tooth movement study in mutant mice

Shalish

Will

Fukai

et al. 2014

The Angle Orthodontist

Self Cite

View full text Add to dashboard Cite

show abstract

“…PC1 is expressed in cells within the osteoblast lineage (18), and skeletal abnormalities have been reported in Pkd1 mutant mouse models (14,15,17,18), but from these generalized lossof-function observations it was not clear if the observed skeletal abnormalities were an indirect consequence of loss of PC1 in multiple tissues or a direct effect of loss of PC1 in osteoblasts. In the present studies, we have addressed this question by using mice had a ϳ25% reduction in Pkd1 expression, whereas Pkd1 flox/m1Bei mice had a 50% reduction but had identical effects on bone, suggests that loss of Pkd1 function in osteoblasts is responsible for the observed reduction in bone mass in both models.…”

Section: Discussionmentioning

confidence: 99%

Conditional Disruption of Pkd1 in Osteoblasts Results in Osteopenia Due to Direct Impairment of Bone Formation

Xiao

Zhang

Cao

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

PC1 (polycystin-1) is a highly conserved, receptor-like multidomain membrane protein widely expressed in various cell types and tissues (1, 2). Mutations of human PKD1 (polycystic kidney disease gene 1) cause autosomal dominant polycystic kidney disease (ADPKD) 2 (3, 4). The genetics of ADPKD is complex, because it is widely held that inactivation of the normal copy of the PKD1 gene by a second somatic mutation in conjunction with the inherited mutation of the other allele is required for renal cyst formation, which occurs in only a subset of the dually affected tubules (5). Although primarily affecting the kidney, ADPKD is also a multisystem disorder (6, 7). Extrarenal manifestations include intracranial and aortic aneurysms and cystic disease of liver and pancreas (8 -11). The biological functions of PC1 are poorly defined in some tissues that express PKD1 transcripts, such as bone. Indeed, the absence of clinically demonstrable skeletal abnormalities in patients with ADPKD initially delayed the investigation of PKD1 function in bone. The apparent lack of abnormalities in other tissues expressing PC1 may arise because of differences in the frequency of a second hit somatic mutation, the presence of other modifying factors that may compensate for lack of PC1 function in other organs (12), or failure to detect more subtle phenotypes. For example, lung was not thought to be affected by PKD1 mutations until computed tomography scans of lungs of ADPKD patients showed a 3-fold increase in the prevalence of bronchiectasis compared with controls (13).Pkd1 is highly expressed in bone, and several mouse models with inactivating mutations of Pkd1 have skeletal abnormalities in the setting of polycystic kidney disease and embryonic lethality (6, 7, 14 -16). Most recently, however, the heterozygous Pkd1 m1Bei mouse, which has an inactivating mutation of Pkd1 and survives to adulthood without polycystic kidney disease, has been shown to develop osteopenia and impaired osteoblastic differentiation (17,18), suggesting that Pkd1 may function in bone. Because homozygous PKD1/Pkd1 mutations in humans and mice are lethal, and most of the existing models are globally Pkd1-deficient, the significance of inactivation of Pkd1 in osteoblasts remains uncertain, and the bone changes might reflect an indirect effect due to loss of PKD1, in the kidney or other tissues.In the current study, to determine if PKD1 in osteoblasts has a direct function in regulating postnatal skeletal functions, we used mouse genetic approaches to conditionally delete Pkd1 in osteoblasts. We demonstrate that conditional deletion of Pkd1 from osteoblasts using Oc-Cre results defective osteoblast function in vivo and in vitro, and osteopenia, indicating that PKD1 has a direct role to regulate osteoblast function and skeletal homeostasis. EXPERIMENTAL PROCEDURES

show abstract

“…Some genes and transcriptional factors specifically regulate neural crest proliferation and apoptosis: Prtg-deficient (protogenin protein) mice show malformation of bones due to increased apoptosis of rostral CNC (Wang et al, 2013). Polycystin-1 (Pkd1) is required for the proliferation of subpopulations of cranial osteochondroprogenitor cells of both mesodermal and neural crest origin during the growth of the skull (Kolpakova-Hart et al, 2008). Deficiencies of Msx1 and Msx2, homeodomain transcription factor, result in defective patterning and survival of the cranial neural crest (Ishii et al, 2005).…”

Section: Neural Crest Proliferation and Apoptosismentioning

confidence: 99%

Contribution of cranial neural crest cells to mouse skull development

Wu¹,

Chen²,

Tian³

et al. 2017

Int. J. Dev. Biol.

View full text Add to dashboard Cite

The mammalian skull vault is a highly regulated structure that evolutionally protects brain growth during vertebrate development. It consists of several membrane bones with different tissue origins (e.g. neural crest-derived frontal bone and mesoderm-derived parietal bone). Although membrane bones are formed through intramembranous ossification, the neural crest-derived frontal bone has superior capabilities for osteoblast activities and bone regeneration via TGF, BMP, Wnt, and FGF signaling pathways. Neural crest (NC) cells are multipotent, and once induced, will follow specific paths to migrate to different locations of the body where they give rise to a diverse array of cell types and tissues. Recent studies using genetic mouse models have greatly advanced our knowledge of NC cell induction, proliferation, migration and differentiation. Perturbations or disruptions of neural crest patterning lead to severe developmental defects or diseases. This review summarizes recent discoveries including novel functions of genes or signaling molecules that are capable of governing developmental processes of neural crest patterning, which may function as a gene regulatory network in controlling skull development. The proposed regulatory network will be important to understand how the signaling pathways and genes converge to regulate osteoblast activities and bone formation, which will be beneficial for the potential identification of molecular targets to prevent or alleviate human diseases or disorders involving defective neural crest development.

show abstract

Growth of cranial synchondroses and sutures requires polycystin-1

Cited by 41 publications

References 48 publications

Role of polycystin-1 in bone remodeling:Orthodontic tooth movement study in mutant mice

Role of polycystin-1 in bone remodeling:Orthodontic tooth movement study in mutant mice

Conditional Disruption of Pkd1 in Osteoblasts Results in Osteopenia Due to Direct Impairment of Bone Formation

Contribution of cranial neural crest cells to mouse skull development

Contact Info

Product

Resources

About