Inhibition of microRNA-222 expression accelerates bone healing with enhancement of osteogenesis, chondrogenesis, and angiogenesis in a rat refractory fracture model

Yoshizuka, Masaaki; Nakasa, Tomoyuki; Kawanishi, Yoshitaka; Hachisuka, Susumu; Furuta, Takeshi; Miyaki, Shigeru; Adachi, Nobuo; Ochi, Mitsuo

doi:10.1016/j.jos.2016.07.021

Cited by 52 publications

(50 citation statements)

References 19 publications

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“…Having demonstrated the inhibition of miR-222 promoted osteogenic and chondrogenic differentiation in vitro, miR-222 has been mixed with atelocollagen and administered in a rat refractory fracture model for in vivo bone healing assessment. [113] Bone union at the fracture site and enhanced capillary density was achieved in miR-222 inhibitor treated groups 8 weeks postimplantation. Overall, this study successfully demonstrated the effect of miR-222 knockdown on acceleration of bone healing by enhancing osteogenesis, chondrogenesis, and angiogenesis.…”

Section: Osteogenesis and Bone Repairmentioning

confidence: 88%

“…[102,106] Whether one of the routes may be better suited for clinical translation remains to be elucidated, although in situ transfecting scaffolds hold greater potential to exist as "off-the-shelf" products. [107] Many distinct scaffold types have been tuned to serve the purpose of miRNA delivery, including several hydrogels, [58,92,106,[108][109][110][111][112][113][114] electrospun fibers, [63,[115][116][117][118] and more prolifically porous or spongy scaffolds. [46,47,50,54,55,96,112,[119][120][121][122][123][124][125][126][127][128][129][130] Before reviewing the details of their applications, summarized in Table 2 and described further in the next section, we will discuss the key characteristics making these materials amenable to miRNA delivery.…”

Section: Scaffolds For Microrna Deliverymentioning

confidence: 99%

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Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Curtin

Castaño

O’Brien

2017

Adv Healthcare Materials

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The field of "regenerative medicine" (RM) was conceptually developed to aid the body's natural capacity to self-repair, a capacity which is impaired with age and in cases of disease or injury. [1] RM is a vast and multifaceted area of medicine, often microRNA-based therapies are an advantageous strategy with applications in both regenerative medicine (RM) and cancer treatments. microRNAs (miRNAs) are an evolutionary conserved class of small RNA molecules that modulate up to one third of the human nonprotein coding genome. Thus, synthetic miRNA activators and inhibitors hold immense potential to finely balance gene expression and reestablish tissue health. Ongoing industrysponsored clinical trials inspire a new miRNA therapeutics era, but progress largely relies on the development of safe and efficient delivery systems. The emerging application of biomaterial scaffolds for this purpose offers spatiotemporal control and circumvents biological and mechanical barriers that impede successful miRNA delivery. The nascent research in scaffold-mediated miRNA therapies translates know-how learnt from studies in antitumoral and genetic disorders as well as work on plasmid (p)DNA/siRNA delivery to expand the miRNA therapies arena. In this progress report, the state of the art methods of regulating miRNAs are reviewed. Relevant miRNA delivery vectors and scaffold systems applied to-date for RM and cancer treatment applications are discussed, as well as the challenges involved in their design. Overall, this progress report demonstrates the opportunity that exists for the application of miRNA-activated scaffolds in the future of RM and cancer treatments.Regenerative Medicine

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Section: Osteogenesis and Bone Repairmentioning

confidence: 88%

Section: Scaffolds For Microrna Deliverymentioning

confidence: 99%

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Curtin

Castaño

O’Brien

2017

Adv Healthcare Materials

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“…miR‐222 is known to be a negative regulator of angiogenesis, a process critical to successful fracture repair. In conjunction with a rat femoral transverse fracture and cauterization of the periosteum at the fracture site, a miR‐222 inhibitor and mimic were each tested (along with a nonfunctional inhibitor negative control) for their effects on fracture repair . Initially, the miR‐222 inhibitor, mimic, and negative control were mixed with atelocollagen and administered into the fracture site (immediately after fracture).…”

Section: Mirnas and Fracture Repairmentioning

confidence: 99%

The Therapeutic Potential of MicroRNAs as Orthobiologics for Skeletal Fractures

Hadjiargyrou

Komatsu

2019

Journal of Bone and Mineral Research

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The repair of a fractured bone is critical to the well‐being of humans. Failure of the repair process to proceed normally can lead to complicated fractures, exemplified by either a delay in union or a complete nonunion. Both of these conditions lead to pain, the possibility of additional surgery, and impairment of life quality. Additionally, work productivity decreases, income is reduced, and treatment costs increase, resulting in financial hardship. Thus, developing effective treatments for these difficult fractures or even accelerating the normal physiological repair process is warranted. Accumulating evidence shows that microRNAs (miRNAs), small noncoding RNAs, can serve as key regulatory molecules of fracture repair. In this review, a brief description of the fracture repair process and miRNA biogenesis is presented, as well as a summary of our current knowledge of the involvement of miRNAs in physiological fracture repair, osteoporotic fractures, and bone defect healing. Further, miRNA polymorphisms associated with fractures, miRNA presence in exosomes, and miRNAs as potential therapeutic orthobiologics are also discussed. This is a timely review as several miRNA‐based therapeutics have recently entered clinical trials for nonskeletal applications and thus it is incumbent upon bone researchers to explore whether miRNAs can become the next class of orthobiologics for the treatment of skeletal fractures.

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“…Enhanced hMSCs-mediated in vivo cartilage repair [32,60] miR-222 Enhanced chondrogenesis and osteogenesis of hMSCs in vitro. Improved angiogenesis and bone union and healing in vivo [102] circRNA-CER Increased expression of collagen II and aggrecan in human OA chondrocytes. Suppression of MMP13 [108] lncRNA-CIR Increased expression of collagen I, II, aggrecan and GAGs production in human OA chondrocytes.…”

Section: Silencing Of Non-coding Rnasmentioning

confidence: 99%

“…Notably, seeding of miR-221-depleted hMSCs in cartilage defects led to enhanced cartilage repair in vivo, providing a proof of concept for the implantation of miRNA-depleted hMSCs for improved cartilage repair. Interestingly, Yoshizuka et al showed that silencing of the paralogue of miR-221, miR-222, promoted chondrogenesis, and osteogenesis of hMSCs, as well as angiogenesis and bone healing in a rat fracture model [102].…”

Section: Silencing Of Non-coding Rnasmentioning

confidence: 99%

Emerging potential of gene silencing approaches targeting anti-chondrogenic factors for cell-based cartilage repair

Lolli

Penolazzi

Narcisi

et al. 2017

Cell. Mol. Life Sci.

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The field of cartilage repair has exponentially been growing over the past decade. Here, we discuss the possibility to achieve satisfactory regeneration of articular cartilage by means of human mesenchymal stem cells (hMSCs) depleted of anti-chondrogenic factors and implanted in the site of injury. Different types of molecules including transcription factors, transcriptional co-regulators, secreted proteins, and microRNAs have recently been identified as negative modulators of chondroprogenitor differentiation and chondrocyte function. We review the current knowledge about these molecules as potential targets for gene knockdown strategies using RNA interference (RNAi) tools that allow the specific suppression of gene function. The critical issues regarding the optimization of the gene silencing approach as well as the delivery strategies are discussed. We anticipate that further development of these techniques will lead to the generation of implantable hMSCs with enhanced potential to regenerate articular cartilage damaged by injury, disease, or aging.

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Inhibition of microRNA-222 expression accelerates bone healing with enhancement of osteogenesis, chondrogenesis, and angiogenesis in a rat refractory fracture model

Abstract: Local administration of miR-222 inhibitor can accelerate bone healing by enhancing osteogenesis, chondrogenesis, and angiogenesis in the rat refractory model.

Cited by 52 publications

References 19 publications

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

The Therapeutic Potential of MicroRNAs as Orthobiologics for Skeletal Fractures

Emerging potential of gene silencing approaches targeting anti-chondrogenic factors for cell-based cartilage repair

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