Prolonged Upright Posture Induces Degenerative Changes in Intervertebral Discs of Rat Cervical Spine

Liang, Qianqian; Cui, Xue‐jun; Xi, Zhijie; Bian, Qin; Hou, Wei; Zhao, Yongjian; Shi, Qi; Wang, Yongjun

doi:10.1097/brs.0b013e3181d2dec2

Cited by 24 publications

(14 citation statements)

References 28 publications

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“…It is well established that physiological mechanical loads are beneficial for disc biology, whereas non-physiological loads can initiate and accelerate disc degeneration [ 11 – 13 ]. Previously, a foreleg amputation-induced rat disc degeneration model showed increased senescent cells within the degenerative disc [ 14 – 16 ]. These studies indirectly indicated that excessive and continuous mechanical compression caused by prolonged upright postures may aggravate cellular senescence within the disc.…”

Section: Introductionmentioning

confidence: 99%

Role of p38–MAPK pathway in the effects of high-magnitude compression on nucleus pulposus cell senescence in a disc perfusion culture

Pang

Zhang

et al. 2017

Bioscience Reports

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Nucleus pulposus (NP) cell senescence is a typical pathological feature within the degenerative intervertebral disc. As a potential inducing and aggregating factor of disc degeneration, mechanical overloading affects disc biology in multiple ways. The present study was to investigate the NP cell senescence-associated phenotype under intermittent high compression in an ex vivo disc bioreactor culture, and the role of the p38–MAPK pathway in this regulatory process. Porcine discs were cultured in culture chambers of a self-developed mechanically active bioreactor and subjected to different magnitudes of dynamic compression (low-magnitude and high-magnitude: 0.1 and 1.3 MPa at a frequency of 1.0 Hz for 2 h per day respectively) for 7 days. Non-compressed discs were used as controls. The inhibitor SB203580 was used to study the role of the p38–MAPK pathway in this process. Results showed that intermittent high-magnitude compression clearly induced senescence-associated changes in NP cells, such as increasing β-galactosidase-positive NP cells, decreasing PCNA-positive NP cells, promoting the formation of senescence-associated heterochromatic foci (SAHF), up-regulating the expression of senescence markers (p16 and p53), and attenuating matrix production. However, inhibition of the p38–MAPK pathway partly attenuated the effects of intermittent high-magnitude (1.3 MPa) compression on those described NP cell senescence-associated parameters. In conclusion, intermittent high-magnitude compression can induce NP cell senescence-associated changes in an ex vivo disc bioreactor culture, and the p38–MAPK pathway is involved in this process.

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Section: Introductionmentioning

confidence: 99%

Role of p38–MAPK pathway in the effects of high-magnitude compression on nucleus pulposus cell senescence in a disc perfusion culture

Pang

Zhang

et al. 2017

Bioscience Reports

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“…This environment elicits a range of pathological responses from NP and AF cells including dysregulation of NP‐marker genes such as ACAN and COL2A1 as well as more general processes such as autophagy, senescence, and apoptosis . Concurrently, degenerative NP and AF cells increase the expression of matrix degrading enzymes including matrix metalloproteinases (MMPs) −1, −3, −7, −9, −10 −13 and a disintegrin and MMP with thrombospondin motifs (ADAMTS) −1, −4, −5, −9, and −15 . This further accelerates loss of type II collagen and PG rich ECM and replacement with fibrous, type I collagen scar‐like tissue.…”

Section: Ivd Structure Function and Degenerationmentioning

confidence: 99%

Therapeutic potential of growth differentiation factors in the treatment of degenerative disc diseases

et al. 2019

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Intervertebral disc (IVD) degeneration is a major contributing factor to chronic low back pain and disability, leading to imbalance between anabolic and catabolic processes, altered extracellular matrix composition, loss of tissue hydration, inflammation, and impaired mechanical functionality. Current treatments aim to manage symptoms rather than treat underlying pathology. Therefore, IVD degeneration is a target for regenerative medicine strategies. Research has focused on understanding the molecular process of degeneration and the identification of various factors that may have the ability to halt and even reverse the degenerative process. One such family of growth factors, the growth differentiation factor (GDF) family, have shown particular promise for disc regeneration in in vitro and in vivo models of IVD degeneration. This review outlines our current understanding of IVD degeneration, and in this context, aims to discuss recent advancements in the use of GDF family members as anabolic factors for disc regeneration. An increasing body of evidence indicates that GDF family members are central to IVD homeostatic processes and are able to upregulate healthy nucleus pulposus cell marker genes in degenerative cells, induce mesenchymal stem cells to differentiate into nucleus pulposus cells and even act as chemotactic signals mobilizing resident cell populations during disc injury repair. The understanding of GDF signaling and its interplay with inflammatory and catabolic processes may be critical for the future development of effective IVD regeneration therapies.

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“…7 The NP matrix consists of an irregular mesh of type II collagen and elastin fibers with abundant and highly hydrophilic proteoglycans, most significantly aggrecan. [8][9][10][11][12] DIVD commonly results in a change from type II to type I collagen and a decrease in proteoglycan content leading to dehydration of the NP, 13 an increase in expression of matrix degrading enzymes, [14][15][16][17] an upregulation of inflammatory cytokines [18][19][20] and an increase in cell senescence and apoptosis. [21][22][23] Adult NP cells cultured in NC cell conditioned media (NCCM) showed an upregulation of aggrecan, type II collagen, CD44, link protein and tissue inhibitor of metalloproteinase 1 (TIMP1).…”

Section: Introductionmentioning

confidence: 99%

An optimized culture system for notochordal cell expansion with retention of phenotype

et al. 2018

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Background Notochordal (NC) cells display therapeutic potential in treating degeneration of the intervertebral disc. However, research on their phenotype and function is limited by low‐cell yields and a lack of appropriate methodology for cell expansion. Utilizing porcine cells, this study aimed to develop an optimized culture system which allows expansion of NC cell populations with retention of phenotype. Methods Post‐natal porcine and foetal human nucleus pulposus tissue was compared histologically and expression of known NC cell marker genes by porcine NC cells was analyzed. Porcine NC cells were isolated from six‐week post‐natal discs and cultured in vitro under varied conditions: (1) DMEM vs αMEM; (2) laminin‐521, fibronectin, gelatin and uncoated tissue culture‐treated polystyrene (TCP); (3) 2% O 2 vs normoxia; (4) αMEM (300 mOsm/L) vs αMEM (400 mOsm/L); (5) surface stiffness of 0.5 and 4 kPa and standard TCP. Adherence, proliferation, morphology and expression of NC cell markers were assessed over a 14‐day culture period. Results Native porcine nucleus pulposus tissue demonstrated similar morphology to human foetal tissue and porcine NC cells expressed known notochordal markers (CD24, KRT8, KRT18, KRT19, and T). Use of αMEM media and laminin‐521‐coated surfaces showed the greatest cell adherence, proliferation and retention of NC cell morphology and phenotype. Proliferation of NC cell populations was further enhanced in hypoxia (2%) and phenotypic retention was improved on 0.5 kPa culture surfaces. Discussion Our model has demonstrated an optimized system in which NC cell populations may be expanded while retaining a notochordal phenotype. Application of this optimized culture system will enable NC cell expansion for detailed phenotypic and functional study, a major advantage over current culture methods described in the literature. Furthermore, the similarities identified between porcine and human NC cells suggest this system will be applicable in human NC cell culture for investigation of their therapeutic potential.

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Prolonged Upright Posture Induces Degenerative Changes in Intervertebral Discs of Rat Cervical Spine

Abstract: Upright stance accelerates cervical disc degeneration in rats.

Cited by 24 publications

References 28 publications

Role of p38–MAPK pathway in the effects of high-magnitude compression on nucleus pulposus cell senescence in a disc perfusion culture

Role of p38–MAPK pathway in the effects of high-magnitude compression on nucleus pulposus cell senescence in a disc perfusion culture

Therapeutic potential of growth differentiation factors in the treatment of degenerative disc diseases

An optimized culture system for notochordal cell expansion with retention of phenotype

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