title: Skeletal diseases caused by mutations that affect collagen structure and function.
abstract: Collagens form critical elements of extracellular matrices that provide mechanical strength to skeletal tissues and serve as a binding platform for cells of bone and cartilage. The formation of collagen-rich extracellular matrices is a complex process that involves intracellular and extracellular steps. Mutations in genes that encode individual chains of triple-helical collagens present in bone and cartilage are associated with heritable diseases of skeletal tissues. In addition, mutations in genes encoding proteins involved in the intracellular and extracellular modifications of collagens are also responsible for developing skeletal abnormalities. In this review, we will summarize the pathomechanisms of molecular and cellular consequences of mutations that alter collagen structure and function. Moreover, we will discuss the prospects and limitations of therapeutic approaches to minimize the effects of mutations that affect collagens of skeletal tissues.
authors.affiliation: Department of Orthopaedic Surgery, Rothman Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: William V
authors.initials: WV
authors.lastname: Arnold
authors.forename: Andrzej
authors.initials: A
authors.lastname: Fertala
mesh_terms: D000818:Animals; D001847:Bone Diseases / Q000235:genetics* / Q000628:therapy; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D000070818:Discoidin Domain Receptors; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D009154:Mutation / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D011975:Receptors, Mitogen / Q000235:genetics
chemical_list: D011975:Receptors, Mitogen; D003094:Collagen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: Bone; Cartilage; Collagen; ER stress; Heritable diseases