Bone morphogenetic protein receptors and activin receptors are highly expressed in ossified ligament tissues of patients with ossification of the posterior longitudinal ligament.
Ossification of the posterior longitudinal ligament (OPLL) is a pathological ossification in the spinal ligament, with formation of ectopic bone mainly through endochondral ossification. Bone morphogenetic proteins (BMPs) and activins are multifunctional proteins that belong to the transforming growth factor-beta superfamily and that have been implicated in the formation of new bone and cartilage. BMPs and activins signal via type I and type II receptors for BMPs (BMPRs) and activins (ActRs), respectively. OP-1/BMP-7 binds to BMPR-II and ActR-II and forms complexes with BMPR-IA and -IB and ActR-I. We studied the expression of BMPR-IA, -IB, and -II, ActR-I, ActR-II, and OP-1/BMP-7 by immunohistochemistry in ossified ligament tissues of patients with OPLL and control ligament tissues from patients with cervical disc herniation. The expression of BMPRs and ActRs was elevated in OPLL compared with controls. Expressions of BMPR-IA, -IB, and -II were observed not only in chondrocytes at the fibrocartilage tissue around the calcified zone but also in fibroblast-like spindle cells at the nonossified ligament. ActR-I and -II were found co-localized in the hypertrophic chondrocytes near the calcified zone and in the ossified tissue. OP-1/BMP-7 was expressed in chondrocytes near the calcified zone. In the control cases, the BMPRs and ActRs were only weakly expressed in the fibrocartilage tissue at the site of ligament attachments to bone and OP-1/BMP-7 was not detected. Enhanced expression of BMPRs at the nonossified ligament in OPLL patients suggests that these cells have a greater potential to differentiate into osteogenic cells than ligament cells from non-OPLL patients. The high expression of BMPRs and ActRs in the ectopic ossified ligament suggests that BMPs and activin may be tightly involved in the pathological ossification process of OPLL.
Yonemori
K
K
Department of Orthopaedic Surgery, Faculty of Medicine, Kagoshima University, Japan.
Imamura
T
T
Ishidou
Y
Y
Okano
T
T
Matsunaga
S
S
Yoshida
H
H
Kato
M
M
Sampath
T K
TK
Miyazono
K
K
ten Dijke
P
P
Sakou
T
T
D029404:Activin Receptors; D000328:Adult; D000368:Aged; D055419:Bone Morphogenetic Protein 7; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D006801:Humans; D017846:Longitudinal Ligaments / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009999:Ossification, Heterotopic / Q000378:metabolism* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000096:biosynthesis* / Q000378:metabolism; D016212:Transforming Growth Factor beta
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors; C498211:BMPR1A protein, human; C498218:BMPR2 protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II