Co-treatment of TGF-β3 and BMP7 is superior in stimulating chondrocyte redifferentiation in both hypoxia and normoxia compared to single treatments

Huang, Xiaobin; Zhong, Leilei; Post, Janine N.; Karperien, Marcel

doi:10.1038/s41598-018-27602-y

Cited by 24 publications

(16 citation statements)

References 41 publications

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“…This is unexpected, since activation of SMAD1/5/8 is generally associated with an OA chondrocyte phenotype and its terminal differentiation. 44 In contrast to its clear hypertrophy-suppressive action on OA chondrocytes, 27 BMP7 has previously been shown to activate SMAD1/5/8 signaling 45 , 46 and inhibit SMAD3 activity. 47 How signaling downstream of different BMPs (e.g., BMP2, BMP4, BMP7, BMP9, etc.)…”

Section: Discussionmentioning

confidence: 99%

Discovery of bone morphogenetic protein 7-derived peptide sequences that attenuate the human osteoarthritic chondrocyte phenotype

Caron

Ripmeester

Akker

et al. 2021

Molecular Therapy - Methods & Clinical Development

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Treatment of osteoarthritis (OA) is mainly symptomatic by alleviating pain to postpone total joint replacement. Bone morphogenetic protein 7 (BMP7) is a candidate morphogen for experimental OA treatment that favorably alters the chondrocyte and cartilage phenotype. Intra-articular delivery and sustained release of a recombinant growth factor for treating OA are challenging, whereas the use of peptide technology potentially circumvents many of these challenges. In this study, we screened a high-resolution BMP7 peptide library and discovered several overlapping peptide sequences from two regions in BMP7 with nanomolar bioactivity that attenuated the pathological OA chondrocyte phenotype. A single exposure of OA chondrocytes to peptides p[63−82] and p[113−132] ameliorated the OA chondrocyte phenotype for up to 8 days, and peptides were bioactive on chondrocytes in OA synovial fluid. Peptides p[63−82] and p[113−132] required NKX3-2 for their bioactivity on chondrocytes and provoke changes in SMAD signaling activity. The bioactivity of p[63−82] depended on specific evolutionary conserved sequence elements common to BMP family members. Intra-articular injection of a rat medial meniscal tear (MMT) model with peptide p[63−82] attenuated cartilage degeneration. Together, this study identified two regions in BMP7 from which bioactive peptides are able to attenuate the OA chondrocyte phenotype. These BMP7-derived peptides provide potential novel disease-modifying treatment options for OA.

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Section: Discussionmentioning

confidence: 99%

Discovery of bone morphogenetic protein 7-derived peptide sequences that attenuate the human osteoarthritic chondrocyte phenotype

Caron

Ripmeester

Akker

et al. 2021

Molecular Therapy - Methods & Clinical Development

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“…Co-IP and Q Extractive mass spectrometry were performed to screen for proteins that bind to SPARCL1 during bovine bovine skeletal muscle-derived satellite cells differentiation (unpublished data). BMP7, as a member of the TGF-β superfamily 32 is secreted into the extracellular space, where it may interact with some cell membrane components or ECM proteins such as SPARCL1. This was verified by Co-IP in C2C12 cells.…”

Section: Discussionmentioning

confidence: 99%

SPARCL1 promotes C2C12 cell differentiation via BMP7-mediated BMP/TGF-β cell signaling pathway

et al. 2019

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The extracellular matrix (ECM) is known to regulate tissue development and cell morphology, movement, and differentiation. SPARCL1 is an ECM protein, but its role in mouse cell differentiation has not been widely investigated. The results of western blotting and immunofluorescence showed that SPARCL1 is associated with the repair of muscle damage in mice and that SPARCL1 binds to bone morphogenetic protein 7 (BMP7) by regulating BMP/transforming growth factor (TGF)-β cell signaling. This pathway promotes the differentiation of C2C12 cells. Using CRISPR/Cas9 technology, we also showed that SPARCL1 activates BMP/TGF-β to promote the differentiation of C2C12 cells. BMP7 molecules were found to interact with SPARCL1 by immunoprecipitation analysis. Western blotting and immunofluorescence were performed to verify the effect of BMP7 on C2C12 cell differentiation. Furthermore, SPARCL1 was shown to influence the expression of BMP7 and activity of the BMP/TGF-β signaling pathway. Finally, SPARCL1 activation was accompanied by BMP7 inhibition in C2C12 cells, which confirmed that SPARCL1 affects BMP7 expression and can promote C2C12 cell differentiation through the BMP/TGF-β pathway. The ECM is essential for muscle regeneration and damage repair. This study intends to improve the understanding of the molecular mechanisms of muscle development and provide new treatment ideas for muscle injury diseases.

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“…[ 48 ] In particular, TGF‐β3 supplementation was previously shown to activate Smad2/3 signaling pathways in cultures of MSC pellets, leading to increased cartilaginous matrix production, including its characteristic components collagen II (Col II), aggrecan, and glycosaminoglycans (GAGs). [ 49,50 ] In alternative to recombinant TGF‐β3 supplementation, here we sought to analyze whether MINP‐2 could capture TGF‐β3 from PL and trigger similar effects on ASCs. After incubating the NPs with PL and washing out loosely adsorbed proteins from the soft corona, they were mixed into hASC suspensions, pelleted, and then cultured in standard medium for 7 days ( Figure a).…”

Section: Resultsmentioning

confidence: 99%

Epitope‐Imprinted Nanoparticles as Transforming Growth Factor‐β3 Sequestering Ligands to Modulate Stem Cell Fate

Teixeira

Domingues

Babo

et al. 2020

Adv Funct Materials

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Growth factors (GFs) are biomolecules with potent biological effects but inherent limitations hinder their potential as therapeutic agents and cell culture supplements in tissue engineering and regenerative medicine (TERM). Biomaterials that sequester endogenous GFs by affinity binding might circumvent such limitations and thus are being increasingly investigated. Here, molecularly imprinted nanoparticles (MINPs) are proposed as specific abiotic ligands for GFs. As a proof of concept, a conformational epitope of transforming growth factor‐β3 (TGF‐β3) is designed and surface imprinted onto polyacrylamide‐based nanoparticles by inverse microemulsion polymerization. It is found that, depending on the polymerization mixture composition, MINPs can recognize and preferentially bind TGF‐β3, either in noncompetitive assays or from a complex human fluid (platelet lysate). Substrates functionalized with MINPs are then used for 2D culture of adipose‐derived stem cells. Remarkably, gene and protein expression profiles show a marked upregulation of SOX‐9, suggesting activation of TGF‐β3 signaling pathways without requiring supplementation with exogenous GF. Likewise, culturing these cells in pellets incorporating MINPs previously incubated with platelet lysate results in higher collagen II‐rich matrix deposition, compared to pellets incorporating non‐imprinted nanoparticles. In summary, results suggest MINPs can be used as cost‐effective, stable, and scalable alternative abiotic GF ligands to guide cell fate in TERM applications.

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Co-treatment of TGF-β3 and BMP7 is superior in stimulating chondrocyte redifferentiation in both hypoxia and normoxia compared to single treatments

Cited by 24 publications

References 41 publications

Discovery of bone morphogenetic protein 7-derived peptide sequences that attenuate the human osteoarthritic chondrocyte phenotype

Discovery of bone morphogenetic protein 7-derived peptide sequences that attenuate the human osteoarthritic chondrocyte phenotype

SPARCL1 promotes C2C12 cell differentiation via BMP7-mediated BMP/TGF-β cell signaling pathway

Epitope‐Imprinted Nanoparticles as Transforming Growth Factor‐β3 Sequestering Ligands to Modulate Stem Cell Fate

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