title: Ectopic mineralization of cartilage and collagen-rich tendons and ligaments in Enpp1asj-2J mice.
abstract: Generalized arterial calcification of infancy (GACI), an autosomal recessive disorder caused by mutations in the ENPP1 gene, manifests with extensive mineralization of the cardiovascular system. A spontaneous asj-2J mutant mouse has been characterized as a model for GACI. Previous studies focused on phenotypic characterization of skin and vascular tissues. This study further examined the ectopic mineralization phenotype of cartilage, collagen-rich tendons and ligaments in this mouse model. The mice were placed on either control diet or the "acceleration diet" for up to 12 weeks of age. Soft connective tissues, such as ear (elastic cartilage) and trachea (hyaline cartilage), were processed for standard histology. Assessment of ectopic mineralization in articular cartilage and fibrocartilage as well as tendons and ligaments which are attached to long bones were performed using a novel cryo-histological method without decalcification. These analyses demonstrated ectopic mineralization in cartilages as well as tendons and ligaments in the homozygous asj-2J mice at 12 weeks of age, with the presence of immature osteophytes displaying alkaline phosphatase and tartrate-resistant acid phosphatase activities as early as at 6 weeks of age. Alkaline phosphatase activity was significantly increased in asj-2J mouse serum as compared to wild type mice, indicating increased bone formation rate in these mice. Together, these data highlight the key role of ENPP1 in regulating calcification of both soft and skeletal tissues.
authors.affiliation: Department of Dermatology and Cutaneous Biology, The Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA.|Department of Dermatology, The Fourth Military Medical University, Xijing Hospital, Xi'an, China.
authors.forename: Jieyu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center for Regenerative Medicine and Skeletal Development, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Nathaniel A
authors.initials: NA
authors.lastname: Dyment
authors.affiliation: Center for Regenerative Medicine and Skeletal Development, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Rowe
authors.affiliation: Department of Dermatology and Cutaneous Biology, The Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Sarah Y
authors.initials: SY
authors.lastname: Siu
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Sundberg
authors.affiliation: Department of Dermatology and Cutaneous Biology, The Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
authors.affiliation: Department of Dermatology and Cutaneous Biology, The Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000166:cytology* / Q000378:metabolism; D002113:Calcification, Physiologic; D002118:Calcium / Q000378:metabolism*; D002356:Cartilage / Q000166:cytology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D008022:Ligaments / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010727:Phosphoric Diester Hydrolases / Q000502:physiology*; D011755:Pyrophosphatases / Q000502:physiology*; D013710:Tendons / Q000166:cytology* / Q000378:metabolism
chemical_list: D003094:Collagen; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases; D002118:Calcium
keywords: Pathology Section; chondrocalcinosis; ectopic mineralization; generalized arterial calcification of infancy; mouse models; tendon and ligament calcification