Uni-axial Cyclic Stretch Induces Cbfa1 Expression in Spinal Ligament Cells Derived from Patients with Ossification of the Posterior Longitudinal Ligament

Abstract Background: The molecular mechanisms of ossification of the posterior longitudinal ligament (OPLL) remains to be elucidated. The aim of the present study was to investigate the autophagy of spinal ligament fibroblasts derived from patients with OPLL and to examine whether autophagy associated gene expression was correlated with the expression of osteogenic differentiation genes. Methods: Expression of autophagy associated genes was detected in 37 samples from 21 OPLL patients and 16 non-OPLL patients. The correlation of autophagy associated gene expression and the expression of osteogenic differentiation genes was analyzed by Pearson’s correlation. The expression of autophagy associated genes of ligament fibroblasts was assessed by reverse transcription-quantitative Polymerase Chain Reaction (RT-qPCR), western blotting and immunofluorescence. The incidence of autophagy was assessed by flow cytometry. After knockdown using small interfering RNA targeting Beclin1, the expression of osteogenic differentiation genes were compared in spinal ligament fibroblasts. Results: In clinical specimens, mRNA expression levels of microtubule-associated protein 1 light chain 3 and Beclin1 were higher in the OPLL group compared with the non-OPLL group. Pearson correlation analysis demonstrated that Beclin1 expression was positively correlated with expression of osteocalcin (OCN) (r=0.8233, P<0.001), alkaline phosphatase, biomineralization associated (ALP) (r=0.7821, P<0.001) and collagen type 1 (COL 1) (r=0.6078, P=0.001). Consistently, the upregulation of autophagy associated genes in ligament fibroblasts from patients with OPLL were further confirmed by western blotting and immunofluorescence. The incidence of autophagy was also increased in ligament fibroblasts from patients with OPLL. Furthermore, knockdown of Beclin1 led to a decrease in the expression of OCN, ALP and COL 1 by 63.2% (P<0.01), 52% (P<0.01) and 53.2% (P<0.01) in ligament fibroblasts from patients with OPLL, respectively. Conclusions: Beclin1-mediated autophagy was involved in the osteogenic differentiation of ligament fibroblasts, and promoted the development of OPLL.

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Incidence of complications in 25 adult patients with X-linked hypophosphatemia

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab282 ◽

2021 ◽

Author(s):

Hajime Kato ◽

Minae Koga ◽

Yuka Kinoshita ◽

Yuki Taniguchi ◽

Hiroshi Kobayashi ◽

...

Keyword(s):

Hearing Impairment ◽

Posterior Longitudinal Ligament ◽

Knee Joints ◽

X Rays ◽

Ectopic Ossification ◽

High Prevalence ◽

Computed Tomography Scans ◽

Male Patients ◽

Anterior Posterior ◽

Spinal Ligament

Abstract Context Adults with X-linked hypophosphatemia (XLH) present complications other than osteomalacia. Objective To describe the incidence and severity of comorbidities in adults with XLH. Design Observational retrospective study. Patients A total of 25 adults with XLH with thorough investigations, including spinal computed tomography scans, X-rays of hip/knee joints and Achilles tendons, abdominal ultrasounds and audiograms. Main outcome measures The index of ossification of the anterior/posterior longitudinal ligament and yellow ligament (OA/OP/OY index) and the sum of OA/OP/OY index (OS index) were utilized to evaluate the severity of spinal ligament ossification. The Kellgren-Lawrence (KL) classification was adopted to evaluate the severity of the hip/knee osteophytes. Results The participants consisted of 13 male patients and 12 female patients from 21 families, with a median age of 43 (range, 18-72) years. In all, 20 patients (80%) showed spinal ligament ossification. The median OA/OP/OY/OS indices were 2 (0-22), 0 (0-15), 6 (0-13) and 12 (0-41), respectively. Hip/knee osteophytes were reported in 24 (96%) and 17 cases (68%). The median KL grade was 3 in the hip joint and 2 in the knee joint, and 18 cases (72%) developed enthesopathy in the Achilles tendon. Nephrocalcinosis and hearing impairment were observed in 18 (72%) and eight (32%) cases. Conclusion This study revealed a high prevalence and severity of ectopic ossification and disclosed the incidence of nephrocalcinosis and hearing impairment in adults with XLH. In cases with severe spinal ligament ossification or noticeable osteophytes around the hip/knee joints, undiagnosed XLH should be considered as a possible underlying condition.

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Thoracic myelopathy secondary to ossification of the spinal ligament

Journal of Neurosurgery ◽

10.3171/jns.1987.66.4.0511 ◽

1987 ◽

Vol 66 (4) ◽

pp. 511-518 ◽

Cited By ~ 114

Author(s):

Kazuo Yonenobu ◽

Sohei Ebara ◽

Keiju Fujiwara ◽

Kazuo Yamashita ◽

Keiro Ono ◽

...

Keyword(s):

Surgical Treatment ◽

Clinical Manifestations ◽

Posterior Longitudinal Ligament ◽

Motor Deficits ◽

Thoracic Myelopathy ◽

Content Type ◽

Atypical Symptoms ◽

Initial Improvement ◽

Upper Thoracic ◽

Spinal Ligament

✓ The authors describe their experience with 26 cases of thoracic myelopathy secondary to hypertrophic ossification of the spinal ligament (posterior longitudinal ligament and/or ligamentum flavum). The clinical manifestations of this condition and results of its surgical treatment are described. The commonest symptoms were numbness or tingling in the legs and feet and gait disturbance. Most of the patients with involvement of the upper thoracic spine showed typical features of thoracic myelopathy: that is, sensory and motor deficits in both the trunk and lower extremities, sphincter disturbance, and exaggerated tendon reflexes. Several patients with involvement of the thoracolumbar junction presented with atypical symptoms of thoracic myelopathy and were sometimes misdiagnosed and treated inappropriately. Surgical treatment, particularly laminectomy, was not always successful. Inconsistencies in the surgical outcome were caused by either operative complications or reversal of the initial improvement during the follow-up period. The results of anterior surgery for the condition were more favorable; however, use of this procedure was rarely indicated.

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Role of Prostaglandin I2 in the Gene Expression Induced by Mechanical Stress in Spinal Ligament Cells Derived from Patients with Ossification of the Posterior Longitudinal Ligament

Journal of Pharmacology and Experimental Therapeutics ◽

10.1124/jpet.102.047142 ◽

2003 ◽

Vol 305 (3) ◽

pp. 818-824 ◽

Cited By ~ 44

Author(s):

Hirotaka Ohishi ◽

Ken-Ichi Furukawa ◽

Koei Iwasaki ◽

Kazumasa Ueyama ◽

Akihiro Okada ◽

...

Keyword(s):

Gene Expression ◽

Mechanical Stress ◽

Posterior Longitudinal Ligament ◽

Prostaglandin I2 ◽

Spinal Ligament

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Acromegaly presenting with myelopathy due to ossification of posterior longitudinal ligament: a case report

BMC Musculoskeletal Disorders ◽

10.1186/s12891-021-04232-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Daisuke Kamakura ◽

Katsunori Fukutake ◽

Kazumasa Nakamura ◽

Shintaro Tsuge ◽

Keiji Hasegawa ◽

...

Keyword(s):

Pituitary Adenoma ◽

Posterior Longitudinal Ligament ◽

High Serum ◽

Posterior Fixation ◽

Facial Features ◽

Thoracic Myelopathy ◽

Lower Extremity Weakness ◽

Main Challenge ◽

Spinal Ligament

Abstract Background Acromegaly is a rare disease caused by high serum levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), often originating from a pituitary adenoma. Spinal and peripheral joint abnormalities are caused by these hormonal hypersecretions. In particular, the response to GH is involved in the onset of ossification of the spinal ligament in vitro, especially ossification of the posterior longitudinal ligament (OPLL). However, because acromegaly and OPLL are rare diseases, we seldom encounter them in combination. To the best of our knowledge in the English-language literature, this is the first reported case of acromegaly presenting with thoracic myelopathy due to OPLL. Case presentation A 47-year-old woman presented with lower extremity weakness and paresthesia, gait disorder, and bladder disorder without any trauma. The patient’s most remarkable symptom was paraplegia, and we diagnosed myelopathy due to cervical and thoracic OPLL. Furthermore, we suspected acromegaly because of the characteristic facial features, and we found a pituitary adenoma by contrast-enhanced MRI. Cervical and thoracic decompression, posterior fixation, and pituitary adenoma resection were performed. Conclusion We report a case of acromegaly that was detected after the diagnosis of OPLL. The main challenge in acromegaly is delayed in diagnosis. Even in this case, the facial features characteristic of acromegaly had appeared at least 9 years ago. Early diagnosis and treatment of acromegaly improve prognosis and reduce exposure to GH and IGF-1 through early intervention and seem to suppress the progression of ligament ossification. Orthopedic surgeons and neurosurgeons need to keep in mind that acromegaly is associated with bone/joint lesions and ossification of the spinal ligament and should aim to diagnose acromegaly early.

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