Possible Roles of Bone Morphogenetic Proteins and Transforming Growth Factor-βs in the Pathogenesis of OPLL and OLF

Abstract

Ossifi cation of the posterior longitudinal ligament (OPLL) and the ligamentum fl avum (OLF) is a pathological condition in the spinal ligament, with heterotopic bone mainly through endochondral ossifi cation. Bone morphogenetic proteins (BMPs) and transforming growth factor-βs, which belongs to the transforming growth factor-β superfamily (TGFβs), have been responsible for new bone and cartilage formation in vivo. The participating regulatory factors in the complex process (e.g., ligands of the TGF-β superfamily and responsive cell types that express their specifi c receptors) may resemble those that lead to pathological ectopic bone formation. Therefore, they might be causative factors in the pathogenesis of OPLL and OLF. Possible mechanisms are as follows: (1) systemic overexpression of BMPs/TGFβs, their receptors, or both in the patients, such as BMP-4 overexpression in fi brodysplasia ossifi cans progressiva [1]; (2) local overexpression of BMPs/TGFβs, their receptors, or both around or in the spinal ligaments; and (3) enhancement of responsiveness to BMPs/TGFβs in the mesenchymal cells around or in the ligaments. Systemic overexpression of BMPs/TGFβs in OPLL or OLF patients has never been reported, but there have been several reports of local overexpression of BMPs/TGFβs, their receptors, or both and of enhancement of responsiveness to BMPs/TGFβs. These data suggest that BMPs/TGFβs may play a signifi cant role in the pathogenesis of OPLL and OLF. This chapter reviews the accumulated information on BMPs/TGFβs in OPLL and OLF and discusses the biological and clinical signifi cance of BMPs/TGFβs. Bone Morphogenetic Proteins and Transforming Growth Factor-bs