Talk:Musculoskeletal System - Bone Development - Revision history

Z8600021 at 03:16, 28 August 2020

2020-08-28T03:16:46Z

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	In response to bone fracture, periosteal progenitor cells proliferate, expand, and differentiate to form cartilage and bone in the fracture callus. These cellular functions require the coordinated activation of multiple transcriptional programs, and the transcriptional regulators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) regulate osteochondroprogenitor activation during endochondral bone development. However, recent observations raise important distinctions between the signaling mechanisms used to control bone morphogenesis and repair. Here, we tested the hypothesis that YAP and TAZ regulate osteochondroprogenitor activation during endochondral bone fracture healing in mice. Constitutive YAP and/or TAZ deletion from Osterix-expressing cells impaired both cartilage callus formation and subsequent mineralization. However, this could be explained either by direct defects in osteochondroprogenitor differentiation after fracture, or by developmental deficiencies in the progenitor cell pool prior to fracture. Consistent with the second possibility, we found that developmental YAP/TAZ deletion produced long bones with impaired periosteal thickness and cellularity. Therefore, to remove the contributions of developmental history, we next generated adult onset-inducible knockout mice (using Osx-CretetOff ) in which YAP and TAZ were deleted prior to fracture, but after normal development. Adult onset-induced YAP/TAZ deletion had no effect on cartilaginous callus formation, but impaired bone formation at 14 days post-fracture (dpf). Earlier, at 4 dpf, adult onset-induced YAP/TAZ deletion impaired the proliferation and expansion of osteoblast precursor cells located in the shoulder of the callus. Further, activated periosteal cells isolated from this region at 4 dpf exhibited impaired osteogenic differentiation in vitro upon YAP/TAZ deletion. Finally, confirming the effects on osteoblast function in vivo, adult onset-induced YAP/TAZ deletion impaired bone formation in the callus shoulder at 7 dpf, prior to the initiation of endochondral ossification. Together, these data show that YAP and TAZ promote the expansion and differentiation of periosteal osteoblast precursors to accelerate bone fracture healing.		In response to bone fracture, periosteal progenitor cells proliferate, expand, and differentiate to form cartilage and bone in the fracture callus. These cellular functions require the coordinated activation of multiple transcriptional programs, and the transcriptional regulators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) regulate osteochondroprogenitor activation during endochondral bone development. However, recent observations raise important distinctions between the signaling mechanisms used to control bone morphogenesis and repair. Here, we tested the hypothesis that YAP and TAZ regulate osteochondroprogenitor activation during endochondral bone fracture healing in mice. Constitutive YAP and/or TAZ deletion from Osterix-expressing cells impaired both cartilage callus formation and subsequent mineralization. However, this could be explained either by direct defects in osteochondroprogenitor differentiation after fracture, or by developmental deficiencies in the progenitor cell pool prior to fracture. Consistent with the second possibility, we found that developmental YAP/TAZ deletion produced long bones with impaired periosteal thickness and cellularity. Therefore, to remove the contributions of developmental history, we next generated adult onset-inducible knockout mice (using Osx-CretetOff ) in which YAP and TAZ were deleted prior to fracture, but after normal development. Adult onset-induced YAP/TAZ deletion had no effect on cartilaginous callus formation, but impaired bone formation at 14 days post-fracture (dpf). Earlier, at 4 dpf, adult onset-induced YAP/TAZ deletion impaired the proliferation and expansion of osteoblast precursor cells located in the shoulder of the callus. Further, activated periosteal cells isolated from this region at 4 dpf exhibited impaired osteogenic differentiation in vitro upon YAP/TAZ deletion. Finally, confirming the effects on osteoblast function in vivo, adult onset-induced YAP/TAZ deletion impaired bone formation in the callus shoulder at 7 dpf, prior to the initiation of endochondral ossification. Together, these data show that YAP and TAZ promote the expansion and differentiation of periosteal osteoblast precursors to accelerate bone fracture healing.


			==2019==
			{{#pmid:30471432}}

			'''SHP2 regulates intramembranous ossification by modifying the TGFβ and BMP2 signaling pathway'''

			SHP2 is a ubiquitously expressed protein tyrosine phosphatase, which is involved in many signaling pathways to regulate the skeletal development. In endochondral ossification, SHP2 is known to modify the osteogenic fate of osteochondroprogenitors and to impair the osteoblastic transdifferentiation of hypertrophic chondrocytes. However, how SHP2 regulates osteoblast differentiation in intramembranous ossification remains incompletely understood. To address this question, we generated a mouse model to ablate SHP2 in the Prrx1-expressing mesenchymal progenitors by using "Cre-loxP"-mediated gene excision and examined the development of calvarial bone, in which the main process of bone formation is intramembranous ossification. Phenotypic characterization showed that SHP2 mutants have severe defects in calvarial bone formation. Cell lineage tracing and in situ hybridization data showed less osteoblast differentiation of mesenchymal cells and reduced osteogenic genes expression, respectively. Further mechanistic studies revealed enhanced TGFβ and suppressed BMP2 signaling in SHP2 ablated mesenchymal progenitors and their derivatives. Our study uncovered the critical role of SHP2 in osteoblast differentiation through intramembranous ossification and might provide a potential target to treat craniofacial skeleton disorders.

	==2018==		==2018==

Z8600021 at 03:13, 28 August 2020

2020-08-28T03:13:43Z

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	'''Endochondral ossification slides:''' [http://vslide1.med.unsw.edu.au/slide.jsp?fn=histology/b12_40xr.fpx&mag=40 Developing bone] \| [http://vslide1.med.unsw.edu.au/slide.jsp?fn=anatomy/ANAT6778.svs&mag=40 Bone, Developing (LS, Femur) Cat H&E]		'''Endochondral ossification slides:''' [http://vslide1.med.unsw.edu.au/slide.jsp?fn=histology/b12_40xr.fpx&mag=40 Developing bone] \| [http://vslide1.med.unsw.edu.au/slide.jsp?fn=anatomy/ANAT6778.svs&mag=40 Bone, Developing (LS, Femur) Cat H&E]

	~~==10 Most Recent Papers==~~
	~~{{10 Most Recent}}~~

	==~~=Bone Development=~~==		==2020==
	~~<pubmed limit=5>Bone~~ Development</~~pubmed>~~
			{{#pmid:32850826}}

			'''Review - New Insights Into Cranial Synchondrosis Development'''

			The synchondroses formed via endochondral ossification in the cranial base are an important growth center for the neurocranium. Abnormalities in the synchondroses affect cranial base elongation and the development of adjacent regions, including the craniofacial bones. In the central region of the cranial base, there are two synchondroses present-the intersphenoid synchondrosis and the spheno-occipital synchondrosis. These synchondroses consist of mirror image bipolar growth plates. The cross-talk of several signaling pathways, including the parathyroid hormone-like hormone (PTHLH)/parathyroid hormone-related protein (PTHrP), Indian hedgehog (Ihh), Wnt/β-catenin, and fibroblast growth factor (FGF) pathways, as well as regulation by cilium assembly and the transcription factors encoded by the RUNX2, SIX1, SIX2, SIX4, and TBX1 genes, play critical roles in synchondrosis development. Deletions or activation of these gene products in mice causes the abnormal ossification of cranial synchondrosis and skeletal elements. Gene disruption leads to both similar and markedly different abnormalities in the development of intersphenoid synchondrosis and spheno-occipital synchondrosis, as well as in the phenotypes of synchondroses and skeletal bones. This paper reviews the development of cranial synchondroses, along with its regulation by the signaling pathways and transcription factors, highlighting the differences between intersphenoid synchondrosis and spheno-occipital synchondrosis.

			{{#pmid:32835424}}

			'''YAP and TAZ promote periosteal osteoblast precursor expansion and differentiation for fracture repair'''

			In response to bone fracture, periosteal progenitor cells proliferate, expand, and differentiate to form cartilage and bone in the fracture callus. These cellular functions require the coordinated activation of multiple transcriptional programs, and the transcriptional regulators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) regulate osteochondroprogenitor activation during endochondral bone development. However, recent observations raise important distinctions between the signaling mechanisms used to control bone morphogenesis and repair. Here, we tested the hypothesis that YAP and TAZ regulate osteochondroprogenitor activation during endochondral bone fracture healing in mice. Constitutive YAP and/or TAZ deletion from Osterix-expressing cells impaired both cartilage callus formation and subsequent mineralization. However, this could be explained either by direct defects in osteochondroprogenitor differentiation after fracture, or by developmental deficiencies in the progenitor cell pool prior to fracture. Consistent with the second possibility, we found that developmental YAP/TAZ deletion produced long bones with impaired periosteal thickness and cellularity. Therefore, to remove the contributions of developmental history, we next generated adult onset-inducible knockout mice (using Osx-CretetOff ) in which YAP and TAZ were deleted prior to fracture, but after normal development. Adult onset-induced YAP/TAZ deletion had no effect on cartilaginous callus formation, but impaired bone formation at 14 days post-fracture (dpf). Earlier, at 4 dpf, adult onset-induced YAP/TAZ deletion impaired the proliferation and expansion of osteoblast precursor cells located in the shoulder of the callus. Further, activated periosteal cells isolated from this region at 4 dpf exhibited impaired osteogenic differentiation in vitro upon YAP/TAZ deletion. Finally, confirming the effects on osteoblast function in vivo, adult onset-induced YAP/TAZ deletion impaired bone formation in the callus shoulder at 7 dpf, prior to the initiation of endochondral ossification. Together, these data show that YAP and TAZ promote the expansion and differentiation of periosteal osteoblast precursors to accelerate bone fracture healing.

	~~===Bone Embryology===~~
	~~<pubmed limit=5>Bone Embryology</pubmed>~~

	==2018==		==2018==

Z8600021 at 01:48, 12 March 2018

2018-03-12T01:48:24Z

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	==2018==		==2018==

			===The emerging role of Hippo signaling pathway in regulating osteoclast formation===

			J Cell Physiol. 2018 Jun;233(6):4606-4617. doi: 10.1002/jcp.26372. Epub 2018 Jan 15.

			Yang W1, Han W1, Qin A2, Wang Z3, Xu J3, Qian Y1.

			Abstract

			A delicate balance between osteoblastic bone formation and osteoclastic bone resorption is crucial for bone homeostasis. This process is regulated by the Hippo signaling pathway including key regulatory molecules RASSF2, NF2, MST1/2, SAV1, LATS1/2, MOB1, YAP, and TAZ. It is well established that the Hippo signaling pathway plays an important part in regulating osteoblast differentiation, but its role in osteoclast formation and activation remains poorly understood. In this review, we discuss the emerging role of Hippo-signaling pathway in osteoclast formation and bone homeostasis. It is revealed that specific molecules of the Hippo-signaling pathway take part in a stage specific regulation in pre-osteoclast proliferation, osteoclast differentiation and osteoclast apoptosis and survival. Upon activation, MST and LAST, transcriptional co-activators YAP and TAZ bind to the members of the TEA domain (TEAD) family transcription factors, and influence osteoclast differentiation via regulating the expression of downstream target genes such as connective tissue growth factor (CTGF/CCN2) and cysteine-rich protein 61 (CYR61/CCN1). In addition, through interacting or cross talking with RANKL-mediated signaling cascades including NF-κB, MAPKs, AP1, and NFATc1, Hippo-signaling molecules such as YAP/TAZ/TEAD complex, RASSF2, MST2, and Ajuba could also potentially modulate osteoclast differentiation and function. Elucidating the roles of the Hippo-signaling pathway in osteoclast development and specific molecules involved is important for understanding the mechanism of bone homeostasis and diseases.
			KEYWORDS:
			Hippo-signaling pathway; bone metabolism; bone resorption; osteoclast formation
			J Cell Physiol. 2018 Jun;233(6):4606-4617. doi: 10.1002/jcp.26372. Epub 2018 Jan 15. Review.
			PMID: 29219182


	===Stresses and strains on the human fetal skeleton during development===		===Stresses and strains on the human fetal skeleton during development===

Z8600021 at 01:25, 30 Ocak 2018

2018-01-30T01:25:12Z

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 ===Bone Embryology===
 <pubmed limit=5>Bone Embryology</pubmed>
 ==2017==

Z8600021 at 23:54, 6 March 2017

2017-03-06T23:54:33Z

← Older revision		Revision as of 10:54, 7 March 2017
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	<pubmed limit=5>Bone Embryology</pubmed>		<pubmed limit=5>Bone Embryology</pubmed>

			==2017==
			===Cell-matrix signals specify bone endothelial cells during developmental osteogenesis===
			Nat Cell Biol. 2017 Mar;19(3):189-201. doi: 10.1038/ncb3476. Epub 2017 Feb 20.

			Langen UH1, Pitulescu ME1, Kim JM1, Enriquez-Gasca R2, Sivaraj KK1, Kusumbe AP1, Singh A1,2, Di Russo J3, Bixel MG1, Zhou B4, Sorokin L3, Vaquerizas JM2, Adams RH1.
			Abstract

			Blood vessels in the mammalian skeletal system control bone formation and support haematopoiesis by generating local niche environments. While a specialized capillary subtype, termed type H, has been recently shown to couple angiogenesis and osteogenesis in adolescent, adult and ageing mice, little is known about the formation of specific endothelial cell populations during early developmental endochondral bone formation. Here, we report that embryonic and early postnatal long bone contains a specialized endothelial cell subtype, termed type E, which strongly supports osteoblast lineage cells and later gives rise to other endothelial cell subpopulations. The differentiation and functional properties of bone endothelial cells require cell-matrix signalling interactions. Loss of endothelial integrin β1 leads to endothelial cell differentiation defects and impaired postnatal bone growth, which is, in part, phenocopied by endothelial cell-specific laminin α5 mutants. Our work outlines fundamental principles of vessel formation and endothelial cell differentiation in the developing skeletal system.
			PMID 28218908 DOI: 10.1038/ncb3476

			http://www.nature.com/ncb/journal/v19/n3/full/ncb3476.html

	==2015==		==2015==

Z8600021 at 06:44, 24 October 2016

2016-10-24T06:44:10Z

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	\| 206		\| 206
	\|}		\|}

			==1983==

			===Morphologic and radiological observations on the earliest bone marrow formation in human embryos and fetuses===
			Acta Pathol Jpn. 1983 May;33(3):439-46.

			Enzan H, Hara H, Izumi T, Ohkita T.

			Abstract

			Morphologic and radiologic studies were undertaken on 26 human embryos and fetuses to determine the stage and site of the earliest bone marrow formation. Up to the 10th week of gestation, primary bone marrow is not present anywhere although the intramembranous ossification occurs in the maxilla and mandible and also in the middle portion of the clavicle. At the 11th week of gestation, X-ray examination showed in two fetuses the bone formation in the clavicle, scapula, maxilla, mandible, and the diaphysis of the long bones. Serial sections of these fetuses revealed that the primary bone marrow occurs first in the middle portion of the clavicle. From a series of our embryological studies, the concept of the mononuclear phagocyte system which involves the bone-marrow-derived monocytic origin of tissue macrophages, is not accepted, at least, on the origin of Kupffer cells in human fetal livers.

			PMID 6624441

Z8600021 at 01:55, 22 March 2016

2016-03-22T01:55:31Z

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	==2011==		==2011==

			===Bone vs. fat: embryonic origin of progenitors determines response to androgen in adipocytes and osteoblasts===

			Bone. 2011 Oct;49(4):662-72. doi: 10.1016/j.bone.2011.06.010. Epub 2011 Jun 17.

			Wiren KM1, Hashimoto JG, Semirale AA, Zhang XW.

			Abstract

			Although androgen is considered an anabolic hormone, the consequences of androgen receptor (AR) overexpression in skeletally-targeted AR-transgenic lines highlight the detrimental effect of enhanced androgen sensitivity on cortical bone quality. A compartment-specific anabolic response is observed only in male and not in female AR3.6-transgenic (tg) mice, with increased periosteal bone formation and calvarial thickening. To identify anabolic signaling cascades that have the potential to increase bone formation, qPCR array analysis was employed to define expression differences between AR3.6-tg and wild-type (WT) periosteal tissue. Notably, categories that were significantly different between the two genotypes included axonal guidance, CNS development and negative regulation of Wnt signaling with a node centered on stem cell pathways. Further, fine mapping of AR3.6-tg calvaria revealed that anabolic thickening in vivo is not uniform across the calvaria, occurring only in frontal and in not parietal bones. Multipotent fraction 1 progenitor populations from both genotypes were cultured separately as frontal bone neural crest stem-like cells (fNCSC) and parietal bone mesenchymal stem-like cells (pMSC). Both osteoblastic and adipogenic differentiation in these progenitor populations was influenced by embryonic lineage and by genotype. Adipogenesis was enhanced in WT fNCSC compared to pMSC, but transgenic cultures showed strong suppression of lipid accumulation only in fNCSC cells. Osteoblastogenesis was significantly increased in transgenic fNCSC cultures compared to WT, with elevated alkaline phosphatase (ALP) activity and induction of mineralization and nodule formation assessed by alizarin red and von Kossa staining. Osteocalcin (OC) and ALP mRNA levels were also increased in fNCSC cultures from AR3.6-tg vs. WT, but in pMSC cultures ALP mRNA levels, mineralization and nodule formation were decreased in AR3.6-tg cells. Expression differences identified by array in long bone periosteal tissue from AR3.6-tg vs. WT were recapitulated in the fNCSC samples while pMSC profiles reflected cortical expression. These observations reveal the opposing effects of androgen signaling on lineage commitment and osteoblast differentiation that is enhanced in cells derived from a neural crest origin but inhibited in cells derived from a mesodermal origin, consistent with in vivo compartment-specific responses to androgen. Combined, these results highlight the complex action of androgen in the body that is dependent on the embryonic lineage and developmental origin of the cell. Further, these data these data suggest that the periosteum surrounding long bone is derived from neural crest.
			Published by Elsevier Inc.
			PMID 21704206

	===Role of GSK-3β in the Osteogenic Differentiation of Palatal Mesenchyme===		===Role of GSK-3β in the Osteogenic Differentiation of Palatal Mesenchyme===

Z8600021 at 05:14, 19 Mayıs 2015

2015-05-19T05:14:46Z

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 ==2014==
 ===Vascularization of primary and secondary ossification centres in the human growth plate===
 BMC Dev Biol. 2014 Aug 28;14(1):36. [Epub ahead of print]

Z8600021 at 02:48, 19 Mayıs 2015

2015-05-19T02:48:38Z

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	{{Talk Page}}		{{Talk Page}}


			[[Bone Development - Intramembranous Ossification]]


	{\|		{\|

Z8600021 at 08:11, 4 February 2015

2015-02-04T08:11:11Z

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 ===Bone Embryology===
 <pubmed limit=5>Bone Embryology</pubmed>
 ==2014==