Classification of Age-Related Changes in Lumbar Intervertebral Discs

Boos, Norbert; Weißbach, Sabine; Rohrbach, Helmut; Weiler, Christoph; Spratt, Kevin F.; Nerlich, Andreas G.

doi:10.1097/01.brs.0000035304.27153.5b

Cited by 174 publications

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“…Female Col9a1 −/− mouse discs were scored for intervertebral disc cell proliferation as no evidence (score = 0; 33%), increased cell density (score = 1; 47%), connection of 2 cells (score = 2; 13%), or small‐sized clones (score = 3; 7%), while female WT mouse discs were scored as no evidence (score = 0; 73%) or increased cell density (score = 1; 27%). Although significant, cell proliferation scores were relatively low on the grading scale (maximum score = 6) (13, 21). Significant differences were not observed in the other categories.…”

Section: Resultsmentioning

confidence: 97%

“…To evaluate spine degeneration in Col9a1 −/− mice, as previously described (13), a histologic processing and grading scheme was used (13, 21). Spines (n = 20) were sectioned in the sagittal plane (∼7 μm thick), with representative sections selected every 140 μm (6 per spine).…”

Section: Methodsmentioning

confidence: 99%

“…Alternate sections were stained with hematoxylin and eosin or Safranin O–fast green. Images were acquired for 2 lumbar discs of each stained section; these were randomized, and 2 blinded graders evaluated end plate and intervertebral disc regions using a scheme described by Boos and coworkers (21). Intervertebral disc degeneration was scored for tears/cleft formations (ordinal rank range 0–4), chondrocyte proliferation (range 0–6), mucoid degeneration (range 0–4), cell death (range 0–4), and granular changes (range 0–4).…”

Section: Methodsmentioning

confidence: 99%

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Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen

Allen¹,

Griffin²,

Rodriguiz³

et al. 2009

Arthritis & Rheumatism

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Objective. In mice with Col9a1 gene inactivation (Col9a1 ؊/؊ ), osteoarthritis (OA) and intervertebral disc degeneration develop prematurely. The aim of this study was to investigate Col9a1 ؊/؊ mice for functional and symptomatic changes that may be associated with these pathologies.Methods. Col9a1 ؊/؊ and wild-type mice were investigated for reflexes, functional impairment (beam walking, pole climbing, wire hang, grip strength), sensorimotor skills (rotarod), mechanical sensitivity (von Frey hair), and thermal sensitivity (hot plate/tail flick). Gait was also analyzed to determine velocity, stride frequency, symmetry, percentage stance time, stride length, and step width. Postmortem, sera obtained from the mice were analyzed for hyaluronan, and their knees and spines were graded histologically for degeneration.Results. Col9a1 ؊/؊ mice had compensatory gait changes, increased mechanical sensitivity, and impaired physical ability. Col9a1 ؊/؊ mice ambulated with gaits characterized by increased percentage stance times and shorter stride lengths. These mice also had heightened mechanical sensitivity and were deficient in contact righting, wire hang, rotarod, and pole climbing tasks. Male Col9a1 ؊/؊ mice had the highest mean serum hyaluronan levels and strong histologic evidence of cartilage erosion. Intervertebral disc degeneration was also detected, with Col9a1 ؊/؊ mice having an increased incidence of disc tears.Conclusion. These data describe a Col9a1 ؊/؊ behavioral phenotype characterized by altered gait, increased mechanical sensitivity, and impaired function. These gait and functional differences suggest that Col9a1 ؊/؊ mice select locomotive behaviors that limit joint loads. The nature and magnitude of behavioral changes were largest in male mice, which also had the greatest evidence of knee degeneration. These findings suggest that Col9a1 ؊/؊ mice present behavioral changes consistent with anatomic signs of OA and intervertebral disc degeneration.Osteoarthritis (OA) and degenerative disc disease (DDD) are common musculoskeletal disorders, and, as chronic conditions, both have large economic costs (1). Clinically, OA and DDD are associated with joint pain, loss of function, and decreased quality of life. A genetic predisposition to musculoskeletal diseases has been suggested as a determinant of individual risk (2,3), and extracellular matrix mutations have been linked to the premature onset of OA and DDD (4-10). Type IX collagen is a heterotrimeric collagen that associates with type II collagen fibrils and contains domains suited to promote extracellular matrix cohesion (11). Type IX collagen mutations are hypothesized to weaken cartilaginous tissues (8). Mice with inactivation of the Col9a1 gene, henceforth referred to as Col9a1 Ϫ/Ϫ mice, do not form functional type IX collagen molecules (12) and experience spontaneous development of premature cartilage degeneration (as early as 3 months) in the intervertebral disc, knee, and temporomandibular joint that worsens with age (up to 12 months) (12-14). It is not...

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Section: Resultsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen

Allen¹,

Griffin²,

Rodriguiz³

et al. 2009

Arthritis & Rheumatism

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“…Зміни в тканинах ГМД оцінено з використанням класифікаційних систем [9,14,15] у нашій модифікації, що надало можливість провести напівкількісне оцінювання (в балах) структурних порушень (табл. 2).…”

Section: матеріал і методиunclassified

“…Таким чином, матеріал ГМД, отриманий після хірургічного лікування 43 пацієнтів (24 жінки, 19 чоловіків) трьох вікових груп (25-44, 45-60, 61-75 років) було проаналізовано методом гісто-логічного аналізу з використанням напівкількісної бальної шкали. Гістопатологічні зміни в ГМД класифікували на підставі розробок, наведених у літературі [9,14,15], та в нашій модифікації. В основу оцінювання ГМД були покладені такі критерії, які, на думку фахівців, є загальними для визначення дегенерації, а саме: проліферація хондроцитів, що супроводжується утворенням великих структур хондронів, формування осередків розшарування та гранулярного розпаду матриксу, щілин і тріщин, осередків хондроґенезу та фрагментів хрящової замикальної пластинки, відламків кісткової тканини, а також ділянок неоваскуляризації.…”

Section: статьunclassified

Histological analysis of vertebral disc herniations in patients with different age groups

Radchenko¹,

Piontkovsky²,

Dedukh³

2018

ORTHOPAEDICS, TRAUMATOLOGY and PROSTHETICS

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1 ДУ «Інститут патології хребта та суглобів ім. проф. М. І. Ситенка НАМН України», Харків 2 КЗ «Рівенська обласна клінічна лікарня». Україна 3 ДУ «Інститут геронтології ім. Д. Ф. Чеботарьова НАМН України», Київ Изучение характера дегенеративных нарушений в структуре межпозвонковых дисков (МПД) и особенностей микроскопической организации грыж у пациентов различного возраста дает возможность связать патоморфологические изменения с клиническими проявлениями. Цель: изучить особенности структурной организации грыж МПД, полученных после хирургического лечения больных различных возрастных групп. Методы: материал грыж МПД, локализованных на уровнях LIII-LIV, LIV-LV и LV-SI, получен после хирургических операций у 43 человек (24 женщины, 19 мужчин) трех возрастных групп: 1-я -25-44 года, 2-я -45-60, 3-я -61-75. Использованы методы гистологии с полуколичественной оценкой (баллы) дегенеративных изменений. Результат: показано, что пол не влияет на выраженность дегенеративных нарушений в грыжах МПД. По отдельным гистологическим признакам выявлены отличительные особенности. Обнаружено, что в 1-й группе в образцах присутствовали в основном хондроны, содержащие более 15 хондроцитов с крупными ядрами, что свидетельствует о пролиферации и гипертрофии. Выраженных деструктивных нарушений матрикса не выявлено. С возрастом дегенеративные изменения в грыжах МПД прогрессируют. Так, количество крупных хондронов было в 1,7 и в 1,4 раза снижено в материале пациентов 2-й группы по сравнению с 1-й. В матриксе увеличились территории со скоплениями фибробластов (в 3 и 3,2 раза у женщин и мужчин), появились небольшие очаги гранулярного распада и хондрогенеза, зоны с повышенной плотностью фибробластов, мелкие костные секвестры (21,4 %). У женщин и мужчин 3-й группы количество хондронов в грыжах МПД было уменьшено в 2,6 и 2,3 раза соответственно по сравнению с 1-й. В матриксе в 2,4 и 2 раза расширились участки разволокнения, в 1,3 и 1,4 -гранулярного распада. Значительные территории занимали очаги хондрогенеза и в 78,6 % случаев выявлены мелкие костные фрагменты. Вывод: с возрастом выраженность деструктивных нарушений в грыжах МПД значительно повышается. Ключевые слова: грыжа межпозвонкового диска, строение, возрастные изменения. © Радченко В. О., Піонтковський В. К., Дєдух Н. В., 2018 Ключові слова: грижа міжхребцевого диска, будова, зміни з віком

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Early‐onset degeneration of the intervertebral disc and vertebral end plate in mice deficient in type IX collagen

Boyd

Richardson

Allen

et al. 2007

Arthritis & Rheumatism

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Objective. Type IX collagen is an important component of the intervertebral disc extracellular matrix. Mutations in type IX collagen are associated with premature disc degeneration in mice and a predisposition to disc disorders in humans. The aim of this study was to assess the prevalence and timeline of intervertebral disc degeneration in mice homozygous for an inactivated Col9a1 gene.Methods. Intact spine segments were harvested from wild-type (WT) and type IX collagen-knockout (Col9a1 Ϫ/Ϫ ) mice at 3, 6, and 12 months of age. Sagittal spine sections were evaluated for evidence of histologic changes, by 2 blinded graders, using a semiquantitative grading method.Results. There was evidence of more degeneration of the disc and end plate in the spines of Col9a1 ؊/؊ mice compared with those of WT controls, at most time points. These findings were significant for the disc region at 3 and 6 months (P < 0.01) and at 12 months (P < 0.10) and for the end plate region only at 6 months (P < 0.10). Degenerative changes in the disc consisted of cellular changes and mucous degeneration. Degeneration in the end plates was associated with more cell proliferation, cartilage disorganization, and new bone formation. Conclusion.A deletion mutation for type IX collagen is associated with connective tissue changes characteristic of musculoskeletal degeneration in bony and cartilaginous tissue regions. Some of the observed changes were similar to cartilage changes in osteoarthritis, while others were more similar to disc degenerative changes in humans. The finding of premature onset of intervertebral disc degeneration in this mouse model may be useful in studies of the pathology and treatment of human disc degeneration.Arthritic degenerative disorders of the spinal intervertebral disc are the most common of the musculoskeletal conditions and have a major impact on society because of the frequency of occurrence and the economic consequences (1). Environmental factors such as physical activity and mechanical loading may explain only a subset of intervertebral disc disorders when compared with inherited genetic factors (2-5). Intervertebral disc disorders and degeneration have been associated with mutations or polymorphisms in genes encoding matrix proteins, including type IX collagen (6) and aggrecan (7), as well as with genes encoding interleukin-1 (IL-1) (8), IL-6 (9), cartilage intermediatelayer protein (10), and vitamin D receptor (11).Mice with genetic mutations in select extracellular matrix proteins, including type II collagen (12) and type I collagen (13), have been shown to acquire structural and functional matrix alterations in the intervertebral disc. In one study, mice carrying an inactivated allele of the Col2a1 gene showed early vertebral end plate ossification and decreased glycosaminoglycan concentration in the vertebrae, end plate, and annulus fibrosus beginning at 1 month, with differences between mutant mice and wild-type (WT) controls no longer evident by the age of 9 months (12). In another study, mice heterozygou...

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Classification of Age-Related Changes in Lumbar Intervertebral Discs

Cited by 174 publications

References 0 publications

Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen

Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen

Histological analysis of vertebral disc herniations in patients with different age groups

Early‐onset degeneration of the intervertebral disc and vertebral end plate in mice deficient in type IX collagen

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