SDF-1/CXCR4 axis coordinates crosstalk between subchondral bone and articular cartilage in osteoarthritis pathogenesis

Qin, Hanjun; Xu, Ting; Wu, Hangtian; Yao, Zilong; Hou, Yilong; Xie, Yongheng; Su, Jianwen; Cheng, Ching‐Li; Yang, Kaifan; Zhang, Xian-Rong; Chai, Yifeng; Yu, Bin; Cui, Zhuang

doi:10.1016/j.bone.2019.05.010

Cited by 43 publications

(39 citation statements)

References 55 publications

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“…Therefore, it may represent a human equivalent to 'osteoblast/chondrocyte progenitors' recently identified in mouse bone marrow using a single-cell RNA sequencing technology 11 . Given the major role of CXCL12 in cell migration 35,49,50 , this DN BMSC subset may facilitate the migration and re-location of BMSCs from blood vessels to the bone formation or remodelling areas, a process believed to be exaggerated in OA-affected bone 51 .…”

Section: Discussionmentioning

confidence: 99%

The osteogenic commitment of CD271+CD56+ bone marrow stromal cells (BMSCs) in osteoarthritic femoral head bone

Ilas

Baboolal

Churchman

et al. 2020

Sci Rep

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Osteoarthritis (OA), the most common joint disorder, is characterised by progressive structural changes in both the cartilage and the underlying subchondral bone. In late disease stages, subchondral bone sclerosis has been linked to heightened osteogenic commitment of bone marrow stromal cells (BMSCs). This study utilised cell sorting and immunohistochemistry to identify a phenotypically-distinct, osteogenically-committed BMSC subset in human OA trabecular bone. Femoral head trabecular bone tissue digests were sorted into CD45-CD271+CD56+CD146-, CD45-CD271+CD56-CD146+ and CD45-CD271+CD56-CD146-(termed double-negative, DN) subsets, and CD45+CD271-hematopoietic-lineage cells served as control. Compared to the CD146+ subset, the CD56+ subset possessed a lower-level expression of adipocyte-associated genes and significantly over 100-fold higher-level expression of many osteoblast-related genes including osteopontin and osteocalcin, whilst the DN subset presented a transcriptionally 'intermediate' BMSC population. All subsets were tri-potential following culture-expansion and were present in control non-OA trabecular bone. However, while in non-OA bone CD56+ cells only localised on the bone surface, in OA bone they were additionally present in the areas of new bone formation rich in osteoblasts and newly-embedded osteocytes. In summary, this study reveals a distinct osteogenically-committed CD271+CD56+ BMSC subset and implicates it in subchondral bone sclerosis in hip OA. CD271+CD56+ subset may represent a future therapeutic target for OA and other bone-associated pathologies. Osteoarthritis (OA) is now recognised as a disease of the whole joint characterised by pathological changes to cartilage, subchondral bone and the synovium 1,2. While the site of initiation is still unclear, subchondral bone changes are an important feature in OA pathophysiology 3. Given the high numbers of bone marrow stromal cells (BMSCs) in the subchondral bone 4-6 , their homeostatic role in health, as well as their potential contribution to the endogenous repair mechanisms in OA is currently an area of considerable interest. Recent studies in OA animal models 7 and in human OA 8,9 point towards an altered commitment of BMSCs in OA progression. BMSCs have been long described as a heterogeneous population of cells 10,11 however, no specific markers capable of identifying and segregating differently-committed BMSC subsets in healthy or OA-affected bone have so far been found. Currently, CD271 is considered as one of the characteristic markers for native human BMSC 12-15. We have previously shown an accumulation of CD271+ BMSCs in the damaged femoral head areas of hip OA patients marked by the presence of bone marrow lesions 8 , which are also known to be associated with cartilage loss and bone sclerosis 16. More recently, we have provided further evidence for increased osteogenic activity in OA subchondral bone, implicating both BMSCs and their terminally differentiated progeny osteocytes in hip OA microstructural changes 9. Specifically, the ...

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Section: Discussionmentioning

confidence: 99%

The osteogenic commitment of CD271+CD56+ bone marrow stromal cells (BMSCs) in osteoarthritic femoral head bone

Ilas

Baboolal

Churchman

et al. 2020

Sci Rep

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“…As a receptor of SDF-1 [7], CXCR4 has been proven to be one of the key factors that are closely involved in the pathogenesis of OA [25,27,28]. e binding of SDF-1 to CXCR4 induces OA cartilage degeneration [28], and it also coordinates the crosstalk between subchondral bone and articular cartilage in OA pathogenesis [29]. In addition, blocking the SDF-1/CXCR4 signaling axis has been reported to be able to inhibit cartilage degeneration in osteoarthritis by CXCR4 antagonists hsa-miR-142-5p: 3′-UCAUCACGAAAGAUGAAAUAC-5′ CXCR4 3′UTR WT: 5′-TACAGUGUACAGUCUUGUAUU-3′…”

Section: Discussionmentioning

confidence: 99%

miR-142-5p as a CXCR4-Targeted MicroRNA Attenuates SDF-1-Induced Chondrocyte Apoptosis and Cartilage Degradation via Inactivating MAPK Signaling Pathway

Xiang

Liu

Yang

et al. 2020

Biochemistry Research International

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Osteoarthritis (OA) is a chronic joint function disorder with characteristics of chondrocytes reduction and extracellular matrix (ECM) components destruction. MicroRNAs (miRNAs) and the SDF-1/CXCR4 axis are essential factors of chondrocyte apoptosis and ECM degeneration. However, very few studies have investigated the correlation between miRNAs and the SDF-1/CXCR4 axis in osteoarthritis so far. Here, through miRNAs microarray and bioinformatics analyses, we identified miR-142-5p as a CXCR4-targeted and dramatically downregulated miRNA in cartilage from OA patients, as well as in SDF-1-induced OA chondrocytes in vitro. In SDF-1-treated primary human OA chondrocytes that were transfected with a miR-142-5p mimic or inhibitor, the expression of CXCR4 was found to be inversely correlated with the expression of miR-142-5p. The dual luciferase reporter assay further verified the target relationship between miR-142-5p and CXCR4. Overexpression of miR-142-5p alleviated OA pathology by suppressing chondrocyte apoptosis, even in CXCR4 overexpressed OA chondrocytes. This was associated with decreased cartilage matrix degradation, reduced cartilage inflammation, and inactivated MAPK signaling pathway. Our study suggests that upregulated expression of CXCR4-targeted miR-142-5p can inhibit apoptosis, inflammation, and matrix catabolism and inactivate the MAPK signaling pathway in OA chondrocytes. Our work provides important insight into targeting miR-142-5p and the SDF-1/CXCR4 axis in OA therapy.

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“…Among these components, SDF-1 and its receptor CXCR4 are crucial for bone marrow retention, mobilization, and are involved in homing and recruitment of stem cells to sites of injured tissues [17]. SDF-1 has been reported to be expressed in a wide range of issues, including those of the heart, skeleton, live, pancreas, endothelium, skin, and spinal cord [20,[32][33][34][35][36]. Recent studies suggest that the interaction of SDF-1 and CXCR4 could partially mediate the tra cking of MSCs to the impaired nucleus in the brain [20,37].…”

Section: Discussionmentioning

confidence: 99%

SDF-1/CXCR4 Axis-mediated Migration of Systematically Transplanted Bone Marrow Mesenchymal Stem Cells Towards the Injured Spinal Cord in a Rat Model

Cai

Yang

Zhao

et al. 2020

Preprint

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Background: Bone marrow-derived mesenchymal stem cells (MSCs) have been shown to migrate to injured spinal cords and promote functional recovery when systemically transplanted into the traumatized spinal cord. However, the the mechanisms underlying their migration to spinal cords are not yet fully understoodMethods: In this study, we systemically transplanted GFP- and luciferase-expressing MSCs into the rat models of spinal cord injury and examined the role of the stromal cell-derived factor 1 (SDF-1)/CXCR4 axis in regulating the migration of transplanted MSCs to spinal cords.Results: After intravenous injection, MSCs migrated to the injured spinal cord where the expression of SDF-1 was increased. Spinal cord recruitment of MSCs was blocked by pre-incubation with an inhibitor of CXCR4. Their presence correlated with morphological and functional recovery. In vitro, SDF-1 or cerebrospinal fluid (CSF) collected from SCI rats promoted a dose-dependent migration of MSCs, which was blocked by an inhibitor of CXCR4 or an SDF-1 antibody.Conclusions: The study suggests that SDF-1/CXCR4 interactions recruit exogenous MSCs to injured spinal cord tissue and may enhance neural regeneration. Modulation of homing capacity may be instrumental in harnessing the therapeutic potential of MSCs.

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SDF-1/CXCR4 axis coordinates crosstalk between subchondral bone and articular cartilage in osteoarthritis pathogenesis

Cited by 43 publications

References 55 publications

The osteogenic commitment of CD271+CD56+ bone marrow stromal cells (BMSCs) in osteoarthritic femoral head bone

The osteogenic commitment of CD271+CD56+ bone marrow stromal cells (BMSCs) in osteoarthritic femoral head bone

miR-142-5p as a CXCR4-Targeted MicroRNA Attenuates SDF-1-Induced Chondrocyte Apoptosis and Cartilage Degradation via Inactivating MAPK Signaling Pathway

SDF-1/CXCR4 Axis-mediated Migration of Systematically Transplanted Bone Marrow Mesenchymal Stem Cells Towards the Injured Spinal Cord in a Rat Model

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SDF-1/CXCR4 axis coordinates crosstalk between subchondral bone and articular cartilage in osteoarthritis pathogenesis

Cited by 43 publications

References 55 publications

The osteogenic commitment of CD271+CD56+ bone marrow stromal cells (BMSCs) in osteoarthritic femoral head bone

The osteogenic commitment of CD271+CD56+ bone marrow stromal cells (BMSCs) in osteoarthritic femoral head bone

miR-142-5p as a CXCR4-Targeted MicroRNA Attenuates SDF-1-Induced Chondrocyte Apoptosis and Cartilage Degradation via Inactivating MAPK Signaling Pathway

SDF-1/CXCR4 Axis-mediated Migration of Systematically&nbsp;Transplanted&nbsp;Bone Marrow Mesenchymal Stem Cells Towards the Injured Spinal Cord in&nbsp;a&nbsp;Rat Model

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SDF-1/CXCR4 Axis-mediated Migration of Systematically Transplanted Bone Marrow Mesenchymal Stem Cells Towards the Injured Spinal Cord in a Rat Model