Current Topics in Pharmacological Research on Bone Metabolism: Molecular Basis of Ectopic Bone Formation Induced by Mechanical Stress

Abstract

Abstract. Ectopic bone formation (EBF) is frequently found in various tissues and affects the prognosis of diseases accompanied by EBF. Although the mechanism of EBF remains unclear, several local factors that influence the progression of EBF have been proposed. We have been focusing on the role of mechanical stress as a local factor in EBF in spinal ligament tissues, that is, ossification of the posterior longitudinal ligament (OPLL), which causes serious neurological deficiencies. Transcriptome analyses revealed that the expressions of several marker genes related to bone remodeling were enhanced after exposure of ligament cells derived from OPLL patients (OPLL cells) to cyclic stretching as a type of mechanical stress. However, no significant alterations in gene expressions were detected after cyclic stretching of ligament cells derived from non-OPLL patients. OPLL cells exposed to cyclic stretching released several autocrine / paracrine factors that are known to mediate bone remodeling. These results suggest that OPLL cells have been transformed into cells that are highly sensitive to mechanical stress, which may induce the progression of OPLL. These observations provide information regarding the role of mechanical stress in the process of EBF.

Association of transforming growth factor-beta 1 gene polymorphism with genetic susceptibility to ossification of the posterior longitudinal ligament in Korean patients

“…Abnormalities of bone metabolism play a role in the pathogenesis of OPLL (Furukawa, 2006). OPLL appears to be a polygenic disease caused by environmental and/or genetic factors, including multiple susceptibility genes.…”

Upregulated expression of PERK in spinal ligament fibroblasts from the patients with ossification of the posterior longitudinal ligament

“…Fibroblasts cells can differentiate into osteoblasts or osteocytes [4,8,9,12,24,28]. This differentiation should be accompanied by an upregulation of several marker genes related to bone formation, such as OCN, ALP and COL I.…”

“…These two processes might differ in terms of the speed of bone formation [6,31]. Although several studies have investigated the osteogenetic characteristic of the spinal ligament fibroblasts from OPLL patients, the intracellular signaling pathways still remain unclear [4,8,9,12,24,28].…”

Mechanical strain induces Cx43 expression in spinal ligament fibroblasts derived from patients presenting ossification of the posterior longitudinal ligament

“…Furthermore, in patients that underwent anterior interbody fusion, the development of ossification evidently slowed and even stopped [17]. Based on these reports, OPLL may tend to progress at the area where mechanical stretch exists, which has been reported by several authors [5,6,18].…”

“…OPLL is a chronic and progressive disease, and clinical symptoms may only occur after the ossified ligaments develop to a certain degree. Although some studies have investigated the role of mechanical strain in OPLL development, the signaling mechanism of such a role remains unclear [5,6].…”