NGF-p75 signaling coordinates skeletal cell migration during bone repair

Xu, Jiajia; Zhao, Li; Tower, Robert J.; Negri, Stefano; Wang, Yiyun; Meyers, Carolyn A.; Sono, Takashi; Qin, Qizhi; Lu, Amy; Xing, Xin; McCarthy, Edward F.; Clemens, Thomas L.; James, Aaron W.

doi:10.1126/sciadv.abl5716

Cited by 41 publications

(44 citation statements)

References 44 publications

(51 reference statements)

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“…After injury, inflammatory signals cause bone regeneration to commence simultaneously with infiltration by sensory nerve fibers. Xu et al [ 42 ] demonstrated that cranial bone injuries stimulate nerve growth factor expression and signaling via p75 in resident osteogenic precursors that affect their migration into the damaged tissue, thus suggesting that nerve growth factor-p75 signaling has potential roles in bone regeneration. Ambrosi et al [ 43 ] reported that intrinsic skeletal stem cell aging in mice alters signaling in the bone marrow niche to a degenerative inflammatory niche, thus leading to poorly regenerated bones because of fragility.…”

Section: Stem Cell Signals In the Regulation Of Tissue Regenerationmentioning

confidence: 99%

The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity

Xiong

Lin

et al. 2022

Military Med Res

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Bone, cartilage, and soft tissue regeneration is a complex spatiotemporal process recruiting a variety of cell types, whose activity and interplay must be precisely mediated for effective healing post-injury. Although extensive strides have been made in the understanding of the immune microenvironment processes governing bone, cartilage, and soft tissue regeneration, effective clinical translation of these mechanisms remains a challenge. Regulation of the immune microenvironment is increasingly becoming a favorable target for bone, cartilage, and soft tissue regeneration; therefore, an in-depth understanding of the communication between immune cells and functional tissue cells would be valuable. Herein, we review the regulatory role of the immune microenvironment in the promotion and maintenance of stem cell states in the context of bone, cartilage, and soft tissue repair and regeneration. We discuss the roles of various immune cell subsets in bone, cartilage, and soft tissue repair and regeneration processes and introduce novel strategies, for example, biomaterial-targeting of immune cell activity, aimed at regulating healing. Understanding the mechanisms of the crosstalk between the immune microenvironment and regeneration pathways may shed light on new therapeutic opportunities for enhancing bone, cartilage, and soft tissue regeneration through regulation of the immune microenvironment.

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Section: Stem Cell Signals In the Regulation Of Tissue Regenerationmentioning

confidence: 99%

The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity

Xiong

Lin

et al. 2022

Military Med Res

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“…Loss of Rictor in osteoblasts impairs bone mass and strength [41,42]. The role of nerve growth factor (NGF) in spinal cord injury repair and bone fracture repair has been extensively studied [43,44]. Previous studies have supported the predicted main regulatory factors Rictor and TEAD1, and suggested that the roles of torin1, DDX5, and CAB39L in the spinal cord and bone warrant further investigation.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis of ipsilateral spinal cord in rats after bone fracture

Wang

Deng

Yuan

et al. 2023

Preprint

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Backgroud: A large amount of research has shown that spinal cord injury causes bone loss and increases fracture risk, while spinal cord injuries caused by fractures and their underlying molecular mechanisms still need further investigation.Methods To investigate the specific changes in the spinal cord after bone fractures, we obtained L4-L5 spinal cord segments from the same side of SD rats with tibial fractures at 0, 3, 7, 14, and 28 days after the fracture. Gene Ontology (GO) enrichment analysis, KEGG pathway analysis, and Ingenuity Pathway Analysis(IPA) were used to analyze the differential gene expression of the genes at different time points .Results Our sequencing results showed that the transcriptional changes in the spinal cord after fracture developed towards the direction of restoring normal physiological function. At 3 and 7 days after fracture, the same-side L4-L5 spinal cord segment showed significant activation of neurodegeneration and central nervous system development, with neurodegeneration activation being most significant at 3 days after fracture and the spinal cord also showing activation of cell survival regulation effects after 7 days of bone fracture. At 14 days after bone fracture, the spinal cord showed significant enrichment in the myelin sheath formation signaling pathway, activation of cell death in the central nervous system, GO terms relating to synaptic function were also significantly enriched. The spinal cord had active gene transcription, protein synthesis, and degradation metabolism processes at these three time points after fracture. At 28 days after fracture, the spinal cord showed recovery of motor function. In addition, a series of important genes in the spinal cord after fracture were differentially expressed, including PCP4 and Krit1. Rictor, TEAD1, torin1, DDX5, CAB39L, and Ngf in the spinal cord may act as upstream master regulators to play a role in fracture repair.Conclusions We speculate that local injury stimulation of the fracture through DRG enters the intermediate neurons of the spinal cord dorsal horn, triggering a series of adaptive changes including activation of neurodegeneration and central nervous system development in the spinal cord, among other changes. With the involvement of important molecules such as PCP4 and Krit1, the physiological function of the spinal cord gradually recovers after fracture, reducing the risk of disuse osteoporosis and promoting fracture repair. This study provides an understanding of the transcriptome changes in the spinal cord following fracture at different time points, and the changes observed across these time points, and screens for important genes that might participate in the regulation of spinal cord fracture healing, providing a sequencing basis for exploring the bidirectional relationship between fracture and the spinal cord.

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“…Both receptors were first expressed on neurons to accompany the function of NGF in regulating neuron survival and growth. Later, they were found expressed on bone linage cells and involved in the bone repair process ( 57 – 59 ). Tomlinson et al ( 60 ) found that the NGF-TrkA axis is of great importance to bone formation under mechanical loading in mice.…”

Section: Signaling Molecules From Nerves To Bone and Their Applicatio...mentioning

confidence: 99%

Nerves within bone and their application in tissue engineering of bone regeneration

Liu

Liu²,

Li³

et al. 2023

Front. Neurol.

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Nerves within bone play an irreplaceable role in promoting bone regeneration. Crosstalk between the nerve system and bone has arisen to the attention of researchers in the field of basic medicine, clinical medicine, and biomaterials science. Successful bone regeneration relies on the appropriate participation of neural system components including nerve fibers, signaling molecules, and neural-related cells. Furthermore, more about the mechanisms through which nerves took part in bone regeneration and how these mechanisms could be integrated into tissue engineering scaffolds were under exploration. In the present review, we aimed to systematically elaborate on the structural and functional interrelationship between the nerve system and bone. In particular, peripheral nerves interact with the bone through innervated axons, multiple neurotrophins, and bone resident cells. Also, we aimed to summarize research that took advantage of the neuro-osteogenic network to design tissue engineering scaffolds for bone repair.

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NGF-p75 signaling coordinates skeletal cell migration during bone repair

Cited by 41 publications

References 44 publications

The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity

The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity

Transcriptomic analysis of ipsilateral spinal cord in rats after bone fracture

Nerves within bone and their application in tissue engineering of bone regeneration

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