Lubricin deficiency in the murine lumbar intervertebral disc results in elevated torsional apparent modulus

Teeple, Erin; Aslani, Koosha; Shalvoy, Matthew R.; Medrano, Jade E.; Zhang, Ling; Machan, Jason T.; Fleming, Braden C.; Jay, Gregory D.

doi:10.1016/j.jbiomech.2015.03.029

Cited by 13 publications

(10 citation statements)

References 15 publications

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“… 132 In addition, the high expression of PRG4 (lubricin) also implies that they play a protective role in reducing shear stress and inflammation and keeping the joint healthy. 133 In contrast, effector chondrocytes were characterized by ossification and shared expression patterns with articular HTCs. 51 Thus, the definitive function of effector chondrocytes is certainly worth future investigation.…”

Section: Discussionmentioning

confidence: 99%

Spatially defined single-cell transcriptional profiling characterizes diverse chondrocyte subtypes and nucleus pulposus progenitors in human intervertebral discs

Zhu

et al. 2021

Bone Res

144

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A comprehensive understanding of the cellular heterogeneity and molecular mechanisms underlying the development, homeostasis, and disease of human intervertebral disks (IVDs) remains challenging. Here, the transcriptomic landscape of 108 108 IVD cells was mapped using single-cell RNA sequencing of three main compartments from young and adult healthy IVDs, including the nucleus pulposus (NP), annulus fibrosus, and cartilage endplate (CEP). The chondrocyte subclusters were classified based on their potential regulatory, homeostatic, and effector functions in extracellular matrix (ECM) homeostasis. Notably, in the NP, a PROCR+ resident progenitor population showed enriched colony-forming unit-fibroblast (CFU-F) activity and trilineage differentiation capacity. Finally, intercellular crosstalk based on signaling network analysis uncovered that the PDGF and TGF-β cascades are important cues in the NP microenvironment. In conclusion, a single-cell transcriptomic atlas that resolves spatially regulated cellular heterogeneity together with the critical signaling that underlies homeostasis will help to establish new therapeutic strategies for IVD degeneration in the clinic.

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Section: Discussionmentioning

confidence: 99%

Spatially defined single-cell transcriptional profiling characterizes diverse chondrocyte subtypes and nucleus pulposus progenitors in human intervertebral discs

Zhu

et al. 2021

Bone Res

144

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“…3C, C'). On the other hand, the expression of proteoglycan 4 (PRG4/ Lubricin), a common marker of healthy IVD (Jay, 1992;Jay and Waller, 2014;Teeple et al, 2015), was remarkably absent in the IVDs of Col2Cre;Prmt5 f/f mutant mice at P10 (Fig. 3D, D').…”

Section: Deletion Of Prmt5 In Osteochondral Progenitors Results In Almentioning

confidence: 98%

Regulation of terminal hypertrophic chondrocyte differentiation inPrmt5mutant mice modeling infantile idiopathic scoliosis

Ramachandran

Vokes

Gray

2019

Preprint

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Idiopathic scoliosis (IS) is the most common type of musculoskeletal defect effecting children and is classified by age of onset, location, and degree of spine curvature. Although rare, the onset of IS during infancy is the more severe and rapidly progressive form of the disease, leading to increased mortality due to significant respiratory compromise. The pathophysiology of IS, in particular for infantile IS, remain elusive. Here, we show that PRMT5 is critical for the regulation of terminal hypertrophic chondrocyte differentiation in the spine and models infantile IS in mouse. Conditional ablation of PRMT5 in osteochondral progenitors led to impaired terminal hypertrophic chondrocyte differentiation and asymmetric defects of endochondral bone formation in the perinatal spine. Analysis of several markers of endochondral ossification revealed increased COLX and Ihh expression and a dramatic reduction of Mmp13 and RUNX2 expression in the intervertebral disc and vertebral growth plate. Furthermore, we demonstrate that PRMT5 function in committed chondrogenic lineages is required for regulation of COLX expression in the adult spine. Together, our results establish PRMT5 as a critical regulator of hypertrophic chondrocyte differentiation and endochondral bone formation in spine development and maintenance.Ducy, P., Zhang, R., Geoffroy, V., Ridall, A. L. and Karsenty, G. (1997). Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89, 747-754. Dy, P., Wang, W., Bhattaram, P., Wang, Q., Wang, L., Ballock, R. T. and Lefebvre, V. (2012). Sox9 directs hypertrophic maturation and blocks osteoblast differentiation of growth plate chondrocytes. Dev Cell 22, 597-609. . AP-1 and Cbfa/runt physically interact and regulate parathyroid hormone-dependent MMP13 expression in osteoblasts through a new osteoblastspecific element 2/AP-1 composite element.

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“…S4D) of the mutant mice. However, the expression of proteoglycan 4 (PRG4/ Lubricin), a common marker of healthy cartilage and IVD (Jay, 1992;Jay and Waller, 2014;Teeple et al, 2015), was remarkably absent in the vertebral growth plate, the IVD endplate and the annulus fibrosus of Col2Cre;Prmt5 f/f mutant mice at P10 ( Fig. 3D,D′; Fig.…”

Section: Loss Of Prmt5 In Osteochondral Progenitors Results In Alterementioning

confidence: 99%

Regulation of terminal hypertrophic chondrocyte differentiation in Prmt5 mutant mice modeling infantile idiopathic scoliosis

Liu

Ramachandran

Vokes

et al. 2019

Disease Models &Amp; Mechanisms

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Idiopathic scoliosis (IS) is the most common type of musculoskeletal defect affecting children worldwide, and is classified by age of onset, location and degree of spine curvature. Although rare, IS with onset during infancy is the more severe and rapidly progressive form of the disease, associated with increased mortality due to significant respiratory compromise. The pathophysiology of IS, in particular for infantile IS, remains elusive. Here, we demonstrate the role of PRMT5 in the infantile IS phenotype in mouse. Conditional genetic ablation of PRMT5 in osteochondral progenitors results in impaired terminal hypertrophic chondrocyte differentiation and asymmetric defects of endochondral bone formation in the perinatal spine. Analysis of these several markers of endochondral ossification revealed increased type X collagen (COLX) and Ihh expression, coupled with a dramatic reduction in Mmp13 and RUNX2 expression, in the vertebral growth plate and in regions of the intervertebral disc in the Prmt5 conditional mutant mice. We also demonstrate that PRMT5 has a continuous role in the intervertebral disc and vertebral growth plate in adult mice. Altogether, our results establish PRMT5 as a critical promoter of terminal hypertrophic chondrocyte differentiation and endochondral bone formation during spine development and homeostasis. This article has an associated First Person interview with the first author of the paper.

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Lubricin deficiency in the murine lumbar intervertebral disc results in elevated torsional apparent modulus

Cited by 13 publications

References 15 publications

Spatially defined single-cell transcriptional profiling characterizes diverse chondrocyte subtypes and nucleus pulposus progenitors in human intervertebral discs

Spatially defined single-cell transcriptional profiling characterizes diverse chondrocyte subtypes and nucleus pulposus progenitors in human intervertebral discs

Regulation of terminal hypertrophic chondrocyte differentiation inPrmt5mutant mice modeling infantile idiopathic scoliosis

Regulation of terminal hypertrophic chondrocyte differentiation in Prmt5 mutant mice modeling infantile idiopathic scoliosis

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