title: Molecular mechanisms of bone formation in spondyloarthritis.
abstract: Spondyloarthritis comprise a group of inflammatory rheumatic diseases characterized by its association to HLA-B27 and the presence of arthritis and enthesitis. The pathogenesis involves both an inflammatory process and new bone formation, which eventually lead to ankylosis of the spine. To date, the intrinsic mechanisms of the pathogenic process have not been fully elucidated, and our progress is remarkable in the identification of therapeutic targets to achieve the control of the inflammatory process, yet our ability to inhibit the excessive bone formation is still insufficient. The study of new bone formation in spondyloarthritis has been mostly conducted in animal models of the disease and only few experiments have been done using human biopsies. The deregulation and overexpression of molecules involved in the osteogenesis process have been observed in bone cells, mesenchymal cells, and fibroblasts. The signaling associated to the excessive bone formation is congruent with those involved in the physiological processes of bone remodeling. Bone morphogenetic proteins and Wnt pathways have been found deregulated in this disease; however, the cause for uncontrolled stimulation remains unknown. Mechanical stress appears to play an important role in the pathological osteogenesis process; nevertheless, the association of other important factors, such as the presence of HLA-B27 and environmental factors, remains uncertain. The present review summarizes the experimental findings that describe the signaling pathways involved in the new bone formation process in spondyloarthritis in animal models and in human biopsies. The role of mechanical stress as the trigger of these pathways is also reviewed.
authors.affiliation: Facultad de Medicina, Universidad Autónoma de Chihuahua, Circuito Universitario Campus II, 31125 Chihuahua, CP, Mexico; Facultad de Ciencias de la Cultura Física, Universidad Autónoma de Chihuahua, 31125 Chihuahua, CP, Mexico.
authors.forename: Susana Aideé
authors.initials: SA
authors.lastname: González-Chávez
authors.affiliation: Facultad de Medicina, Universidad Autónoma de Chihuahua, Circuito Universitario Campus II, 31125 Chihuahua, CP, Mexico; Facultad de Ciencias de la Cultura Física, Universidad Autónoma de Chihuahua, 31125 Chihuahua, CP, Mexico.
authors.forename: Celia María
authors.initials: CM
authors.lastname: Quiñonez-Flores
authors.affiliation: Facultad de Medicina, Universidad Autónoma de Chihuahua, Circuito Universitario Campus II, 31125 Chihuahua, CP, Mexico. Electronic address: dr.cesarpacheco@gmail.com.
authors.forename: César
authors.initials: C
authors.lastname: Pacheco-Tena
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D015796:HLA-B27 Antigen / Q000235:genetics*; D006801:Humans; D008297:Male; D008967:Molecular Biology; D010012:Osteogenesis / Q000235:genetics*; D018570:Risk Assessment; D015398:Signal Transduction; D025241:Spondylarthritis / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D019485:Bone Morphogenetic Proteins; D015796:HLA-B27 Antigen
keywords: Ankylosis; Mechanosensing; Osteogenesis; Signaling pathways