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Maurizio Pacifici, PH.D.
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Dr. Pacifici serves on the Scientific and Medical Advisory Board of the MHE Research Foundation
Research authored by Dr. Pacifici
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List of Publications via PubMed
(NIH National Library of Medicine)
Research authored by Dr. Pacifici
Click the tab and a window will appear.
List of Publications via PubMed
(NIH National Library of Medicine)
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National Library of Medicine, Directory of Health Organizations (SIS) website, as well as the link for Patient
Information on The Diseases Database a cross-referenced index of human disease, and the Intute: health & life
sciences a free online service providing access to the very best Web resources for education and research
located in the UK
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Dr. Pacifici's research
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Conditional Kif3a ablation causes abnormal hedgehog signaling topography, growth plate
dysfunction, and excessive bone and cartilage formation during mouse skeletogenesis
Development 2007 134: 2183-2193.
Eiki Koyama1,, Blanche Young1, Motohiko Nagayama1, Yoshihiro Shibukawa1,*, Motomi Enomoto-
Iwamoto1, Masahiro Iwamoto1, Yukiko Maeda2, Beate Lanske2, Buer Song3,, Rosa Serra3 and
Maurizio Pacifici1,
1 Department of Orthopaedic Surgery, Thomas Jefferson University College of Medicine,
Philadelphia, PA 19107, USA.
2 Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02138,
USA.
3 Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
The motor protein Kif3a and primary cilia regulate important developmental processes, but their
roles in skeletogenesis remain ill-defined. Here we created mice deficient in Kif3a in cartilage and
focused on the cranial base and synchondroses. Kif3a deficiency caused cranial base growth
retardation and dysmorphogenesis, which were evident in neonatal animals by anatomical and
micro-computed tomography (µCT) inspection. Kif3a deficiency also changed synchondrosis growth
plate organization and function, and the severity of these changes increased over time.
By postnatal day (P)7, mutant growth plates lacked typical zones of chondrocyte proliferation and
hypertrophy, and were instead composed of chondrocytes with an unusual phenotype
characterized by strong collagen II (Col2a1) gene expression but barely detectable expression of
Indian hedgehog (Ihh), collagen X (Col10a1), Vegf (Vegfa), MMP-13 (Mmp13) and osterix (Sp7).
Concurrently, unexpected developmental events occurred in perichondrial tissues, including
excessive intramembranous ossification all along the perichondrial border and the formation of
ectopic cartilage masses.
Looking for possible culprits for these latter processes, we analyzed hedgehog signalling
topography and intensity by monitoring the expression of the hedgehog effectors Patched 1 and
Gli1, and of the hedgehog-binding cell-surface component syndecan 3. Compared with controls,
hedgehog signaling was quite feeble within mutant growth plates as early as P0, but was actually
higher and was widespread all along mutant perichondrial tissues.
Lastly, we studied postnatal mice deficient in Ihh in cartilage; their cranial base defects only
minimally resembled those in Kif3a-deficient mice. In summary, Kif3a and primary cilia make unique
contributions to cranial base development and synchondrosis growth plate function.
Their deficiency causes abnormal topography of hedgehog signaling, growth plate dysfunction, and
un-physiologic responses and processes in perichondrial tissues, including ectopic cartilage
formation and excessive intramembranous ossification.
Key words: Kif3a, Primary cilia, Cranial base synchondroses, Hedgehog signaling, Syndecans,
Growth plate, Intramembranous ossification, Ectopic cartilage, Exostoses, Mouse
Abstract 2005 MHE Conference
Syndecans: Cell Surface Modulators of Growth Plate Chondrocyte Behavior and Function
Maurizio Pacifici Department of Orthopaedic Surgery,
Thomas Jefferson University College of Medicine, Philadelphia, PA 19107
Syndecans are single-pass integral membrane components that serve as co-receptors for growth
factors and cytokines and can elicit signal transduction via their cytoplasmic tails. We will present
studies from our group on syndecan biology and function in the growth plates of developing long
bones in chick and mouse embryos. Gain- and loss-of-function data indicate that syndecan-3 has
important roles in restricting mitotic activity to the proliferative zone of growth plate and may do so
in close cooperation and interaction with the signaling molecule Indian hedgehog (Ihh), and that
syndecan-2 may participate in growth plate-associated ossification. Biochemical and protein-
modeling data suggest a dimeric/oligomeric configuration for syndecan-3 on the chondrocyte’s cell
surface. Analyses of embryos mis-expressing syndecan-3 or lacking Ihh provide further clues on
syndecan-3/Ihh interdependence and interrelationships.
The data and the conclusions reached provide insights into mechanisms fine-tuning chondrocyte
proliferation and function and ossification events in the developing and growing skeleton and into
how abnormalities in these fundamental mechanisms may subtend human congenital pathologies,
including osteochondromas in hereditary multiple exostoses syndrome.
dysfunction, and excessive bone and cartilage formation during mouse skeletogenesis
Development 2007 134: 2183-2193.
Eiki Koyama1,, Blanche Young1, Motohiko Nagayama1, Yoshihiro Shibukawa1,*, Motomi Enomoto-
Iwamoto1, Masahiro Iwamoto1, Yukiko Maeda2, Beate Lanske2, Buer Song3,, Rosa Serra3 and
Maurizio Pacifici1,
1 Department of Orthopaedic Surgery, Thomas Jefferson University College of Medicine,
Philadelphia, PA 19107, USA.
2 Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02138,
USA.
3 Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
The motor protein Kif3a and primary cilia regulate important developmental processes, but their
roles in skeletogenesis remain ill-defined. Here we created mice deficient in Kif3a in cartilage and
focused on the cranial base and synchondroses. Kif3a deficiency caused cranial base growth
retardation and dysmorphogenesis, which were evident in neonatal animals by anatomical and
micro-computed tomography (µCT) inspection. Kif3a deficiency also changed synchondrosis growth
plate organization and function, and the severity of these changes increased over time.
By postnatal day (P)7, mutant growth plates lacked typical zones of chondrocyte proliferation and
hypertrophy, and were instead composed of chondrocytes with an unusual phenotype
characterized by strong collagen II (Col2a1) gene expression but barely detectable expression of
Indian hedgehog (Ihh), collagen X (Col10a1), Vegf (Vegfa), MMP-13 (Mmp13) and osterix (Sp7).
Concurrently, unexpected developmental events occurred in perichondrial tissues, including
excessive intramembranous ossification all along the perichondrial border and the formation of
ectopic cartilage masses.
Looking for possible culprits for these latter processes, we analyzed hedgehog signalling
topography and intensity by monitoring the expression of the hedgehog effectors Patched 1 and
Gli1, and of the hedgehog-binding cell-surface component syndecan 3. Compared with controls,
hedgehog signaling was quite feeble within mutant growth plates as early as P0, but was actually
higher and was widespread all along mutant perichondrial tissues.
Lastly, we studied postnatal mice deficient in Ihh in cartilage; their cranial base defects only
minimally resembled those in Kif3a-deficient mice. In summary, Kif3a and primary cilia make unique
contributions to cranial base development and synchondrosis growth plate function.
Their deficiency causes abnormal topography of hedgehog signaling, growth plate dysfunction, and
un-physiologic responses and processes in perichondrial tissues, including ectopic cartilage
formation and excessive intramembranous ossification.
Key words: Kif3a, Primary cilia, Cranial base synchondroses, Hedgehog signaling, Syndecans,
Growth plate, Intramembranous ossification, Ectopic cartilage, Exostoses, Mouse
Abstract 2005 MHE Conference
Syndecans: Cell Surface Modulators of Growth Plate Chondrocyte Behavior and Function
Maurizio Pacifici Department of Orthopaedic Surgery,
Thomas Jefferson University College of Medicine, Philadelphia, PA 19107
Syndecans are single-pass integral membrane components that serve as co-receptors for growth
factors and cytokines and can elicit signal transduction via their cytoplasmic tails. We will present
studies from our group on syndecan biology and function in the growth plates of developing long
bones in chick and mouse embryos. Gain- and loss-of-function data indicate that syndecan-3 has
important roles in restricting mitotic activity to the proliferative zone of growth plate and may do so
in close cooperation and interaction with the signaling molecule Indian hedgehog (Ihh), and that
syndecan-2 may participate in growth plate-associated ossification. Biochemical and protein-
modeling data suggest a dimeric/oligomeric configuration for syndecan-3 on the chondrocyte’s cell
surface. Analyses of embryos mis-expressing syndecan-3 or lacking Ihh provide further clues on
syndecan-3/Ihh interdependence and interrelationships.
The data and the conclusions reached provide insights into mechanisms fine-tuning chondrocyte
proliferation and function and ossification events in the developing and growing skeleton and into
how abnormalities in these fundamental mechanisms may subtend human congenital pathologies,
including osteochondromas in hereditary multiple exostoses syndrome.