Growth and differentiation of a long bone in limb development, repair and regeneration

Egawa, Shiro; Miura, Shotaro; Yokoyama, Hitoshi; Endo, Tetsuro; Tamura, Koji

doi:10.1111/dgd.12136

Cited by 42 publications

(38 citation statements)

References 149 publications

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“…Linear growth of long bones results from endochondral bone formation, in which cartilaginous growth is replaced by ossified bone at the growth plate. This process is governed by a complex set of interactions among GH, IGF-I, 35 thyroid hormone, 35 sex steroids, 36 and glucocorticoids, as well as promotion by Wnt signaling. 37 Our laboratory recently reported decreased canonical Wnt signaling in CFTR −/− murine osteoblasts, 38 suggesting another intrinsic mechanism for poor growth and osteopenia in CF.…”

Section: Discussionmentioning

confidence: 99%

Growth in Prepubertal Children With Cystic Fibrosis Treated With Ivacaftor

et al. 2017

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BACKGROUND AND OBJECTIVES Cystic fibrosis (CF) is known for its impact on the lung and pancreas of affected individuals; however, impaired growth is also a common complication. We hypothesized that targeting the biological defect in the CF transmembrane conductance regulator (CFTR) protein may impact growth outcomes. METHODS In this post hoc analysis, we assessed linear growth and weight in 83 children (aged 6–11) enrolled in 2 clinical trials, the longitudinal-observation GOAL study and the placebo-controlled ENVISION study, to evaluate the effects of ivacaftor, a CFTR potentiator. We calculated height and weight z scores and height and weight growth velocities (GVs). RESULTS In ivacaftor-treated children in GOAL, height and weight z scores increased significantly from baseline to 6 months (increases of 0.1 [P < .05] and 0.26 [P < .0001], respectively); height GV increased significantly from 3 to 6 months (2.10 cm/y increase [P < .01]). In ivacaftor-treated children in ENVISION, height and weight z scores increased significantly from baseline to 48 weeks (increases of 0.17 [P < .001] and 0.35 [P < .001], respectively). Height and weight GVs from baseline to 48 weeks were also significantly higher with ivacaftor than with placebo (differences of 1.08 cm/y [P < .05] and 3.11 kg/y [P < .001], respectively). CONCLUSIONS Ivacaftor treatment in prepubescent children may help to address short stature and altered GV in children with CF; results from these analyses support the existence of an intrinsic defect in the growth of children with CF that may be ameliorated by CFTR modulation.

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Section: Discussionmentioning

confidence: 99%

Growth in Prepubertal Children With Cystic Fibrosis Treated With Ivacaftor

et al. 2017

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“…Formation of new bone happens through endochondral ossification, 78 which is a recapitulation of the developmental process in which cartilage is initially formed and then replaced with bone tissue. 79 Bone regrowth is critically dependent on growth factors such as BMP2 for chondrogenesis 80 and Gdf5 for joint formation. 81 Furthermore, apoptosis 78 is necessary for the replacement of cartilage by mineralized bone.…”

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confidence: 99%

Looking Ahead to Engineering Epimorphic Regeneration of a Human Digit or Limb

Quijano

Lynch

Allan

et al. 2016

Tissue Engineering Part B: Reviews

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Approximately 2 million people have had limb amputations in the United States due to disease or injury, with more than 185,000 new amputations every year. The ability to promote epimorphic regeneration, or the regrowth of a biologically based digit or limb, would radically change the prognosis for amputees. This ambitious goal includes the regrowth of a large number of tissues that need to be properly assembled and patterned to create a fully functional structure. We have yet to even identify, let alone address, all the obstacles along the extended progression that limit epimorphic regeneration in humans. This review aims to present introductory fundamentals in epimorphic regeneration to facilitate design and conduct of research from a tissue engineering and regenerative medicine perspective. We describe the clinical scenario of human digit healing, featuring published reports of regenerative potential. We then broadly delineate the processes of epimorphic regeneration in nonmammalian systems and describe a few mammalian regeneration models. We give particular focus to the murine digit tip, which allows for comparative studies of regeneration-competent and regeneration-incompetent outcomes in the same animal. Finally, we describe a few forward-thinking opportunities for promoting epimorphic regeneration in humans.

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“…little or no cartilage [19,20,37]. In lizards, frogs and salamanders, the injured periosteum has a broad chondrogenic potential [11,15,21,22], and this enhanced chondrogenesis may be related to the mechanical stimulus derived from the free movement of the fractured lizard bones in the injured areas of bone since no containment or ligature of the injured bones was made.…”

Section: Knee Regeneration Is Supported By Resident Progenitor Chondrmentioning

confidence: 99%

“…Regeneration of cartilaginous cells in injured bones and knees of lizards is a remarkable case of cartilage regeneration in amniotes, in comparison to the limited cartilage regeneration detected in mammals [11][12][13][14][15][16][17][18][19][20]. In the latter, the injured periosteum gives rise to a fibro-connective tissue and to some new chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

“…Later, new bone derives from endosteum and bone marrow, which give rise to osteoblasts that directly ossify forming lamellar bone [19]. Even more pronounced in amphibians than in lizards, the cartilaginous tissue can regenerate more abundantly following bone fracture or some injuries in the epiphyses [11,20,21]. However large injuries or the complete removal of the epiphyses also in newts often determines lack of regeneration, an unexpected result considering the broad regeneration of a complete limb with the knee or elbow in these amphibians after limb amputation [21,22].…”

Section: Introductionmentioning

confidence: 99%

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Proliferating Cells in Knee Epiphyses of Lizards Allow for Somatic Growth and Regeneration after Damage

Alibardi

2017

JFMK

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After bone damage, fracture or amputation, lizards regenerate a variable mass of cartilaginous and fibro-cartilaginous tissues, depending from the anatomical site and intensity of inflammation. Aside tail and vertebrae, also long bones and knee epiphyses can regenerate a relative large mass of cartilage after injury. Regeneration is likely related to the persistence of stem cells in growing centers of these bones, localized in the epiphyses of femur, tibia and fibula. The epiphyses form ossified secondary centers in adults but a few progenitor cells remain in the articular cartilage and growth plate, allowing a continuous growth during most lifetime of lizards. The present Review indicates that putative progenitor/stem cells, identified by long labeling retaining of 5-bromo-deoxy-uridine (5BrdU) and immunolocalization of telomerase, remain localized in the articular cartilage and growth plates of the femur and tibia. These cells are re-activated after limited epiphyses damage or amputation of the distal part of the femur or tibia-fibula, and can re-form cartilaginous epiphyses. Regenerating chondrocytes show an intense proliferation and the production of new extracellular matrix components such as collagen VI, chondroitin sulfate proteoglycan, and hyaluronate receptors. The molecular factors at the origin of the chondrogenic potential of the articular cartilage, growth plates, and the periosteum in lizard bones remain to be studied.

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Growth and differentiation of a long bone in limb development, repair and regeneration

Cited by 42 publications

References 149 publications

Growth in Prepubertal Children With Cystic Fibrosis Treated With Ivacaftor

Growth in Prepubertal Children With Cystic Fibrosis Treated With Ivacaftor

Looking Ahead to Engineering Epimorphic Regeneration of a Human Digit or Limb

Proliferating Cells in Knee Epiphyses of Lizards Allow for Somatic Growth and Regeneration after Damage

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