New functions for the proprioceptive system in skeletal biology

Blecher, Ronen; Heinemann-Yerushalmi, Lia; Assaraf, Eran; Konstantin, Nitzan; Cope, Timothy C.; Bewick, Guy S.; Banks, Robert W.; Zelzer, Elazar

doi:10.1098/rstb.2017.0327

Cited by 47 publications

(35 citation statements)

References 109 publications

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“…Finding similar joint abnormalities in mutants for the proprioceptive system regulators Runx3 and Egr3 confirms the role of this system in hip joint morphogenesis. Overall, this work expands our emerging concept 50 and firmly establishes the proprioceptive system as a central regulator of skeletal integrity and Piezo2 as a key component in this regulation (Fig. 10).…”

Section: Discussionsupporting

confidence: 68%

Piezo2 expressed in proprioceptive neurons is essential for skeletal integrity

et al. 2020

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In humans, mutations in the PIEZO2 gene, which encodes for a mechanosensitive ion channel, were found to result in skeletal abnormalities including scoliosis and hip dysplasia. Here, we show in mice that loss of Piezo2 expression in the proprioceptive system recapitulates several human skeletal abnormalities. While loss of Piezo2 in chondrogenic or osteogenic lineages does not lead to human-like skeletal abnormalities, its loss in proprioceptive neurons leads to spine malalignment and hip dysplasia. To validate the non-autonomous role of proprioception in hip joint morphogenesis, we studied this process in mice mutant for proprioceptive system regulators Runx3 or Egr3. Loss of Runx3 in the peripheral nervous system, but not in skeletal lineages, leads to similar joint abnormalities, as does Egr3 loss of function. These findings expand the range of known regulatory roles of the proprioception system on the skeleton and provide a central component of the underlying molecular mechanism, namely Piezo2.

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Section: Discussionsupporting

confidence: 68%

Piezo2 expressed in proprioceptive neurons is essential for skeletal integrity

et al. 2020

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“…The observation that the strong VM-VL correlation was consistent across task conditions might suggest that these patterns are produced by lower-level sensorimotor systems, potentially within the spinal cord. For example, last order spinal interneurons might branch to activate both VM and VL motoneurons (15,55) or be strongly coordinated by feedback from sensory afferents (56) conveying information about patellar loading via joint receptors (57,58) or muscle proprioceptors (59,60). However, previous work has suggested that the strong covariation between VM and VL motor units is due to both cortical and spinal systems (15,16), suggesting that this covariation may result from distributed processing in multiple areas of the CNS.…”

Section: Discussionmentioning

confidence: 99%

Coordination amongst quadriceps muscles suggests neural regulation of internal joint stresses, not simplification of task performance

Alessandro

Barroso

Prashara

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Many studies have demonstrated covariation between muscle activations during behavior, suggesting that muscles are not controlled independently. According to one common proposal, this covariation reflects simplification of task performance by the nervous system so that muscles with similar contributions to task variables are controlled together. Alternatively, this covariation might reflect regulation of low-level aspects of movements that are common across tasks, such as stresses within joints. We examined these issues by analyzing covariation patterns in quadriceps muscle activity during locomotion in rats. The three monoarticular quadriceps muscles (vastus medialis [VM], vastus lateralis [VL], and vastus intermedius [VI]) produce knee extension and so have identical contributions to task performance; the biarticular rectus femoris (RF) produces an additional hip flexion. Consistent with the proposal that muscle covariation is related to similarity of muscle actions on task variables, we found that the covariation between VM and VL was stronger than their covariations with RF. However, covariation between VM and VL was also stronger than their covariations with VI. Since all vastii have identical actions on task variables, this finding suggests that covariation between muscle activity is not solely driven by simplification of overt task performance. Instead, the preferentially strong covariation between VM and VL is consistent with the control of internal joint stresses: Since VM and VL produce opposing mediolateral forces on the patella, the high positive correlation between their activation minimizes the net mediolateral patellar force. These results provide important insights into the interpretation of muscle covariations and their role in movement control.

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“…The upright posture is made possible by proprioceptive system based on cortical, subcortical, and medullary integration of multisensorial information, especially somesthetic input (Munoz-Rubke et al, 2017 ; Sim et al, 2018 ). Proprioceptive system provides direct information on position and movements of body segments (Blecher et al, 2018 ). The gait parameters of AIS patients were investigated, and somatosensory dysfunction in AIS patients showed to have an impact on dynamic balance control (Lao et al, 2008 ).…”

Section: The Function Of the Lbx1 Gene In Interneuron Developmentmentioning

confidence: 99%

The Susceptibility and Potential Functions of the LBX1 Gene in Adolescent Idiopathic Scoliosis

et al. 2021

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Genome-wide association studies have identified many susceptibility genes for adolescent idiopathic scoliosis (AIS). However, most of the results are hard to be replicated in multi-ethnic populations. LBX1 is the most promising candidate gene in the etiology of AIS. We aimed to appraise the literature for the association of LBX1 gene polymorphisms with susceptibility and curve progression in AIS. We also reviewed the function of the LBX1 gene in muscle progenitor cell migration and neuronal determination processes. Three susceptibility loci (rs11190870, rs625039, and rs11598564) near the LBX1 gene, as well as another susceptibility locus (rs678741), related to LBX1 regulation, have been successfully verified to have robust associations with AIS in multi-ethnic populations. The LBX1 gene plays an essential role in regulating the migration and proliferation of muscle precursor cells, and it is known to play a role in neuronal determination processes, especially for the fate of somatosensory relay neurons. The LBX1 gene is the most promising candidate gene in AIS susceptibility due to its position and possible functions in muscle progenitor cell migration and neuronal determination processes. The causality between susceptibility loci related to the LBX1 gene and the pathogenesis of AIS deserves to be explored with further integrated genome-wide and epigenome-wide association studies.

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New functions for the proprioceptive system in skeletal biology

Cited by 47 publications

References 109 publications

Piezo2 expressed in proprioceptive neurons is essential for skeletal integrity

Piezo2 expressed in proprioceptive neurons is essential for skeletal integrity

Coordination amongst quadriceps muscles suggests neural regulation of internal joint stresses, not simplification of task performance

The Susceptibility and Potential Functions of the LBX1 Gene in Adolescent Idiopathic Scoliosis

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