Anabolic Effects of Peniel 2000, a Peptide That Regulates TGF-β1 Signaling on Intervertebral Disc Degeneration

Kwon, Young Joon; Lee, Je–Wook; Moon, Eunsoo; Chung, Yeon Gu; Kim, Ok-Soon; Kim, Hae-Jin

doi:10.1097/brs.0b013e31827aa896

Cited by 22 publications

(21 citation statements)

References 29 publications

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“…In this study western blots for aggrecan and its fragments suggest increased aggrecan breakdown by MMPs and ADAMTS in the inner AF of injured IVDs while injection of TGFβ3 during discectomy prevented aggrecan breakdown and helped to maintain the ECM structure. In addition to our findings, others have previously demonstrated the anabolic potential of TGFβ on ECM homeostasis [25-28]. TGFβ isoforms in combination with dexamethasone could inhibit the expression of catabolic genes such as ADAMTS-5 or members of the MMP family [23,27].…”

Section: Discussionsupporting

confidence: 78%

Detrimental effects of discectomy on intervertebral disc biology can be decelerated by growth factor treatment during surgery: a large animal organ culture model

Illien-Jünger

Purmessur

et al. 2014

The Spine Journal

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BACKGROUND CONTEXT Lumbar discectomies are common surgical interventions that treat radiculopathy by removing herniated and loose intervertebral disc (IVD) tissues. However, remaining IVD tissue can continue to degenerate resulting in long-term clinical problems. Little information is available on the effects of discectomy on IVD biology. Currently no treatments exist that can suspend or reverse the degeneration of the remaining IVD. PURPOSE To improve knowledge how discectomy procedures influence IVD physiology and to assess the potential of growth-factor treatment as an augmentation during surgery STUDY DESIGN To determine effects of discectomy on IVDs with and without TGFβ3 augmentation using bovine IVD organ culture. METHODS This study determined effects of discectomy with and without TGFβ3 injection using 1, 6, and 19 days organ culture experiments. Treated IVDs were injected with 0.2μg TGFβ3 in 20μl PBS+BSA into several locations of the discectomy site. Cell viability, gene expression, nitric-oxide release, IVD height, aggrecan degradation, and proteoglycan content were determined. RESULTS Discectomy significantly increased cell death, aggrecan degradation and nitric-oxide release in healthy IVDs. TGFβ3 injection treatment prevented or mitigated those effects for the 19 days culture period. CONCLUSIONS Discectomy procedures induced cell death, catabolism and nitric-oxide production in healthy IVDs, and we conclude that post-discectomy degeneration is likely to be associated with cell death and matrix degradation. TGFβ3 injection augmented discectomy procedures by acting to protect IVD tissues by maintaining cell viability, limiting matrix degradation and suppressing nitric-oxide. We conclude that discectomy procedures can be improved with injectable therapies at the time of surgery although further in vivo and human studies are required.

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Section: Discussionsupporting

confidence: 78%

Detrimental effects of discectomy on intervertebral disc biology can be decelerated by growth factor treatment during surgery: a large animal organ culture model

Illien-Jünger

Purmessur

et al. 2014

The Spine Journal

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“…NP cells had typical chondrocytic features, suggesting reversal or blockage of the degenerative process. These histologic features of rejuvenated degenerated disc cells have been also described previously (3, 6, 7). …”

Section: Discussionsupporting

confidence: 84%

Resveratrol Has Anabolic Effects on Disc Degeneration in a Rabbit Model

Kwon

2013

J Korean Med Sci

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This study was done to evaluate whether injections of resveratrol, a natural compound found in the skin of grapes, had anabolic effects on degenerated intervertebral discs in a rabbit model. Two non-continuous lumbar discs were punctured in rabbits to induce disc degeneration. Four weeks and 6 weeks after puncture, the rabbits were treated by injections with dimethylsulfoxide (DMSO) or resveratrol. At 4, 8, and 16 weeks after initial injection, rabbits were sacrificed and the spine was extracted for magnetic resonance image (MRI), mRNA expression, and histological staining. Resveratrol treatment resulted in stronger signal intensity in T2-weighted images. MRI grade showed significantly lower in the resveratrol group than the DMSO group (P = 0.039). In the resveratrol group, aggrecan gene expression was significantly increased than that in the DMSO group at 16 weeks after injection (P = 0.027). MMP-13 mRNA levels in the resveratrol group were significantly decreased than those in the DMSO group at 8 and 16 weeks (P = 0.006 and P = 0.048, respectively). In hematoxylin and eosin stain, resveratrol-treated discs showed the features of regeneration. Histologic grade revealed improvement in resveratrol-treated discs, compared with DMSO-treated discs (P = 0.024). These anabolic effects on degenerated discs indicate that resveratrol is a promising candidate for treatment of degenerative disc disease.

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“…39,40,59–63 One group has previously shown that inhibition of TGFβ can prevent DDD, which was attributed to a change in pSmad1/5/8 to pSmad 2/3 downstream signaling. 64 The various effects of TGFβ are likely related to the concentration of TGFβ. Our results demonstrated that pathologic mechanical loading on the spine drove aberrant overactivation of TGFβ, resulting in DDD.…”

Section: Discussionmentioning

confidence: 99%

Mechanosignaling activation of TGFβ maintains intervertebral disc homeostasis

Bian

Jain

et al. 2017

Bone Res

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Intervertebral disc (IVD) degeneration is the leading cause of disability with no disease-modifying treatment. IVD degeneration is associated with instable mechanical loading in the spine, but little is known about how mechanical stress regulates nucleus notochordal (NC) cells to maintain IVD homeostasis. Here we report that mechanical stress can result in excessive integrin αvβ6-mediated activation of transforming growth factor beta (TGFβ), decreased NC cell vacuoles, and increased matrix proteoglycan production, and results in degenerative disc disease (DDD). Knockout of TGFβ type II receptor (TβRII) or integrin αv in the NC cells inhibited functional activity of postnatal NC cells and also resulted in DDD under mechanical loading. Administration of RGD peptide, TGFβ, and αvβ6-neutralizing antibodies attenuated IVD degeneration. Thus, integrin-mediated activation of TGFβ plays a critical role in mechanical signaling transduction to regulate IVD cell function and homeostasis. Manipulation of this signaling pathway may be a potential therapeutic target to modify DDD.

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Anabolic Effects of Peniel 2000, a Peptide That Regulates TGF-β1 Signaling on Intervertebral Disc Degeneration

Abstract: A novel peptide, P2K, regulating TGF-β1 signaling had an anabolic effect on bovine IVD cells and rabbit degenerated discs. The results suggest that P2K has considerable potential as a treatment of degenerative disc disease.

Cited by 22 publications

References 29 publications

Detrimental effects of discectomy on intervertebral disc biology can be decelerated by growth factor treatment during surgery: a large animal organ culture model

Detrimental effects of discectomy on intervertebral disc biology can be decelerated by growth factor treatment during surgery: a large animal organ culture model

Resveratrol Has Anabolic Effects on Disc Degeneration in a Rabbit Model

Mechanosignaling activation of TGFβ maintains intervertebral disc homeostasis

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