Pathologic Mechanism of Experimental Scoliosis in Pinealectomized Chickens

Machida, Masafumi; Dubousset, Jean; Satoh, Takako; Murai, Ichiro; Wood, Kirkham B.; Yamada, Thoru; Junnosuke, Ryu

doi:10.1097/00007632-200109010-00006

Cited by 55 publications

(36 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In animal models of idiopathic scoliosis, such as the chick experimental pinealectomy model, the development of idiopathic scoliosis-like changes has been associated with reduced levels of serum melatonin. Furthermore, administration of melatonin has been shown to prevent the development of scoliosis in both chick and rodent models [35,36]. However, in humans, studies have predominantly reported no difference in serum melatonin levels in patients with or without AIS [5,56], suggesting there would unlikely be any benefit to melatonin supplementation for patients with AIS.…”

Section: Intrinsic Factors Of the Ais Spinal Musculoskeletal System Smentioning

confidence: 99%

Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression

Ede

Jones

2016

International Orthopaedics (SICOT)

View full text Add to dashboard Cite

Adolescent idiopathic scoliosis (AIS) is now considered to be a multifactorial heterogeneous disease, with recent genomic studies supporting the role of intrinsic factors in contributing to the onset of disease pathology and curve progression. Understanding the key molecular signalling pathways by which these intrinsic factors mediate AIS pathology may facilitate the development of pharmacological therapeutics and the identification of predictive markers of progression. The heterogenic nature of AIS has implicated multiple tissue types in the disease pathophysiology, including spinal bone, intervertebral disc and paraspinal muscles. In this review, we highlight some of the mechanisms and intrinsic molecular regulators within these different tissue types and review the evidence for their involvement in AIS pathology.

show abstract

Section: Intrinsic Factors Of the Ais Spinal Musculoskeletal System Smentioning

confidence: 99%

Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression

Ede

Jones

2016

International Orthopaedics (SICOT)

View full text Add to dashboard Cite

show abstract

“…Those above had no radiograph or were not referred that surgical and pharmacological manipulation of laboratory animals (e.g. rabbits [69], chickens [70,71]) can produce a scoliosis similar to the human form, but what else could it resemble? A spine is either straight or it is crooked, and the variation in morphology between species is limited by the underlying structural anatomical homology.…”

Section: Aetiologymentioning

confidence: 99%

Scoliosis: a review

et al. 2007

View full text Add to dashboard Cite

Scoliosis, lateral curvature of the spine, has been studied since Hippocrates' time, but remains a disputed subject in orthopaedic surgery, because of its several varieties, unknown cause and unpredictable course. A review of 30 years' experience in a paediatric orthopaedic unit was undertaken to clarify the problem. Patient records, collected prospectively, were examined to demonstrate the incidence, prevalence, extent, course and outcome of the commonest variety, adolescent idiopathic scoliosis. Reference was made to the results of previously published studies. Records from a school screening programme showed that, while slight degrees of spinal curvature were widely prevalent in the community, these were of no clinical significance and major cosmetic deformity was rare: only 8 in 10,000 adolescent girls had Cobb angles of 40 degrees or more and only half of these underwent surgical correction. Evidence to support non-operative treatment could not be demonstrated and it did not reduce the incidence of surgical intervention. Because the course of scoliosis did not seem to correspond with much published work, or with current hypotheses of aetiology, a rethinking of the whole subject is advocated. An alternative model of pathogenesis deriving from developmental biology was proposed. While advances in surgical methods have been significant, the core problems of aetiology and natural history remain. Until they are resolved, all conclusions on management must be provisional. This is where innovative thinking needs to be directed.

show abstract

“…Pinealectomy resulted in a 100 % rate of deformity in all experiments if animals were rendered free of melatonin, the major product of the pineal gland [13,14]. Furthermore, these investigators demonstrated that development of scoliosis could be prevented by the replantation of the pineal gland in skeletal muscle or by the administration of melatonin as a replacement therapy [12], which however, could not be replicated by others [15,16]. In addition to chickens, scoliosis can be produced in pinealectomized rats and a melatonin deficient strain of mice (C57Bl6) as well, provided that they are forced to attain a bipedal posture by amputation of the forelimbs and tails [17,18].…”

Section: Introductionmentioning

confidence: 99%

“…This model was suggested by the work of Dubousset and co-workers [9] and further improved by Machida and co-workers [10][11][12]. This group of work has demonstrated that pinealectomy produced scoliosis in chickens if the surgery was performed shortly after hatching.…”

Section: Introductionmentioning

confidence: 99%

Selective estrogen receptor modulation prevents scoliotic curve progression: radiologic and histomorphometric study on a bipedal C57Bl6 mice model

et al. 2013

View full text Add to dashboard Cite

Purpose Previous work has suggested that progression of experimental scoliotic curves in pinealectomized chicken and bipedal C57BL6 mice models may be prevented and reversed with Tamoxifen treatment. Raloxifene is another Selective Estrogen Receptor Modulator (SERM) with estrogen agonist effects on bone and increases bone density but with fewer side effects on humans. To investigate whether scoliosis progression in bipedal C57Bl6 mice model could be prevented with SERM treatment and the mechanisms associated with this effect. Methods Eighty C57BL6 mice were rendered bipedal and divided into Tamoxifen (TMX), Raloxifene (RLX) and control groups. TMX and RLX groups received orally administered TMX and RLX for 40 weeks. Anteroposterior X-ray imaging and histomorphometric analysis (at 20th and 40th weeks) were performed. Results At 20th week, TMX and RLX groups displayed higher rates (p = 0.033, p = 0.029) and larger curve magnitudes (p = 0.018). At 40th week, curve rates were similar between the groups but the curve magnitudes in TMX and RLX groups were smaller (p = 0.001). Histomorphometry revealed that treated animals had higher trabecular density (p = 0.04), lower total intervertebral disc (p = 0.038) and growth plate volumes (p = 0.005) and smaller vertebral bodies (p = 0.016). Conclusions Treatment with TMX or RLX did not reduce the incidence of scoliosis but decreased the curve magnitudes at 40 weeks. The underlying mechanism associated with the decrease in curve magnitudes may be the early maturation of growth plates, thereby possible deceleration of the growth rate of the vertebral column and increase in bone density. RLX is as effective as TMX in preventing the progression of scoliotic curves in melatonin deficient bipedal mice.

show abstract

Pathologic Mechanism of Experimental Scoliosis in Pinealectomized Chickens

Cited by 55 publications

References 36 publications

Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression

Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression

Scoliosis: a review

Selective estrogen receptor modulation prevents scoliotic curve progression: radiologic and histomorphometric study on a bipedal C57Bl6 mice model

Contact Info

Product

Resources

About