CCL2 is a critical mechano‐responsive mediator in crosstalk between osteoblasts and bone mesenchymal stromal cells

Yao, Zilong; Chen, Pengyu; Fan, Liuyi; Chen, Peisheng; Zhang, Xianrong; Yu, Bin

doi:10.1096/fj.202002808rr

Cited by 12 publications

(16 citation statements)

References 58 publications

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“…TGF-β) attract stromal-derived mesenchymal cells to the sites of repair. CCL2 produced by osteoblastic cells is also thought to stimulate recruitment of osteoprogenitors cells ( 80 , 81 ). These precursor cells cover the resorbed bone surface.…”

Section: Stimulation Of Bone Formationmentioning

confidence: 99%

Impact of the host response and osteoblast lineage cells on periodontal disease

Zhou

Graves²

2022

Front. Immunol.

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Periodontitis involves the loss of connective tissue attachment and alveolar bone. Single cell RNA-seq experiments have provided new insight into how resident cells and infiltrating immune cells function in response to bacterial challenge in periodontal tissues. Periodontal disease is induced by a combined innate and adaptive immune response to bacterial dysbiosis that is initiated by resident cells including epithelial cells and fibroblasts, which recruit immune cells. Chemokines and cytokines stimulate recruitment of osteoclast precursors and osteoclastogenesis in response to TNF, IL-1β, IL-6, IL-17, RANKL and other factors. Inflammation also suppresses coupled bone formation to limit repair of osteolytic lesions. Bone lining cells, osteocytes and periodontal ligament cells play a key role in both processes. The periodontal ligament contains cells that exhibit similarities to tendon cells, osteoblast-lineage cells and mesenchymal stem cells. Bone lining cells consisting of mesenchymal stem cells, osteoprogenitors and osteoblasts are influenced by osteocytes and stimulate formation of osteoclast precursors through MCSF and RANKL, which directly induce osteoclastogenesis. Following bone resorption, factors are released from resorbed bone matrix and by osteoclasts and osteal macrophages that recruit osteoblast precursors to the resorbed bone surface. Osteoblast differentiation and coupled bone formation are regulated by multiple signaling pathways including Wnt, Notch, FGF, IGF-1, BMP, and Hedgehog pathways. Diabetes, cigarette smoking and aging enhance the pathologic processes to increase bone resorption and inhibit coupled bone formation to accelerate bone loss. Other bone pathologies such as rheumatoid arthritis, post-menopausal osteoporosis and bone unloading/disuse also affect osteoblast lineage cells and participate in formation of osteolytic lesions by promoting bone resorption and inhibiting coupled bone formation. Thus, periodontitis involves the activation of an inflammatory response that involves a large number of cells to stimulate bone resorption and limit osseous repair processes.

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Section: Stimulation Of Bone Formationmentioning

confidence: 99%

Impact of the host response and osteoblast lineage cells on periodontal disease

Zhou

Graves²

2022

Front. Immunol.

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“…Furthermore, mechanical strain increased the secretion of chemokines and the recruitment of MSCs to bone surface, promoting bone formation [81]. Recent findings have also detected links between induction of endosteal progenitors and mechanical loading-induced growth factors released from osteoblastic cells [80]. As tibial bones receive increased axial loading [81], we can assume that these benefit the most from application of osteogenic factors after fracture.…”

Section: Discussionmentioning

confidence: 96%

“…A possible explanation to this finding could be that the relationship between tibial bone structure and axial mechanical loading may provide an exceptional biomechanical environment for growth factor activity. Mechanical loading is a significant factor of bone remodelling and the absence of mechanical signals was accompanied by increased bone resorption and reduced bone formation [77][78][79][80]. Furthermore, mechanical strain increased the secretion of chemokines and the recruitment of MSCs to bone surface, promoting bone formation [81].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Efficacy and Safety of Osteoinductive Factors and Cellular Therapies for Long Bone Fractures and Non-Unions: A Meta-Analysis and Systematic Review

Kaspiris

Hadjimichael

Vasiliadis

et al. 2022

JCM

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Background: Long bone fractures display significant non-union rates, but the exact biological mechanisms implicated in this devastating complication remain unclear. The combination of osteogenetic and angiogenetic factors at the fracture site is an essential prerequisite for successful bone regeneration. The aim of this study is to investigate the results of the clinical implantation of growth factors for intraoperative enhancement of osteogenesis for the treatment of long bone fractures and non-unions. Methods: A systematic literature review search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed and Web of Science databases from the date of inception of each database through to 10 January 2022. Specific inclusion and exclusion criteria were applied in order to identify relevant studies reporting on the treatment of upper and lower limb long bone non-unions treated with osteoinductive or cellular factors. Results: Overall, 18 studies met the inclusion criteria and examined the effectiveness of the application of Bone Morphogenetic Proteins-2 and -7 (BMPs), platelet rich plasma (PRP) and mesenchymal stem cells (MSCs). Despite the existence of limitations in the studies analysed (containing mixed groups of open and close fractures, different types of fractures, variability of treatment protocols, different selection criteria and follow-up periods amongst others), their overall effectiveness was found significantly increased in patients who received them compared with the controls (I2 = 60%, 95% CI = 1.59 [0.99–2.54], Z =1.93, p = 0.05). Conclusion: Administration of BMP-2 and -7, PRP and MSCs were considered effective and safe methods in fracture treatment, increasing bone consolidation, reducing time to repair and being linked to satisfactory postoperative functional scores.

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“…Based on this data and on previous studies showing that catecholamines can increase cytokine production in immune cells ( 42 , 43 ), we hypothesize that myeloid cell-derived catecholamines in an autocrine manner facilitate myeloid cytokine secretion and that the reduced expression of pro-and anti-inflammatory cytokines as a consequence of the TH-KO in myeloid cells activates a feedback loop inducing proliferation of these cells. Reduced cytokine/chemokine levels might further contribute to reduced osteoblasts numbers, since CCL2 was shown to mediate mechano-responsiveness of osteoblasts and, therefore, osteogenesis ( 44 ). Further, IL-6 was demonstrated to have a dual role in osteoblastogenesis based on activation of IL-6 classic or trans-signaling, but especially during fracture healing IL-6 signaling was shown to be important for bone formation ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

Myeloid cell-derived catecholamines influence bone turnover and regeneration in mice

Kühn¹,

Haffner‐Luntzer²,

Kempter³

et al. 2022

Front. Endocrinol.

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Catecholamine signaling is known to influence bone tissue as reuptake of norepinephrine released from sympathetic nerves into bone cells declines with age leading to osteoporosis. Further, b-adrenoceptor-blockers like propranolol provoke osteoprotective effects in osteoporotic patients. However, besides systemic adrenal and sympathetic catecholamine production, it is also known that myeloid cells can synthesize catecholamines, especially under inflammatory conditions. To investigate the effects of catecholamines produced by CD11b + myeloid cells on bone turnover and regeneration, a mouse line with specific knockout of tyrosine hydroxylase, the rate-limiting enzyme of catecholamine synthesis, in CD11b + myeloid cells (TH flox/flox /CD11b-Cre + , referred to as TH CD11b-Cre ) was generated. For bone phenotyping, male mice were sacrificed at eight and twelve weeks of age and harvested bones were subjected to bone length measurement, micro-computed tomography, fluorescence-activated cell sorting of the bone marrow, gene expression analysis, histology and immunohistochemistry. Support for an age-dependent influence of myeloid cell-derived catecholamines on bone homeostasis is provided by the fact that twelve-week-old, but not eight-week-old TH CD11b-Cre mice, developed an osteopenic phenotype and showed increased numbers of neutrophils and T lymphocytes in the bone marrow, while CCL2, IL-6, IL-4 and IL-10 mRNA expression was reduced in sorted myeloid bone marrow cells. To investigate the influence of myeloid cell-derived catecholamines on fracture healing, mice received a diaphyseal femur osteotomy. Three days post-fracture, immunohistochemistry revealed an increased number of macrophages, neutrophils and cytotoxic T lymphocytes in the fracture hematoma of TH CD11b-Cre mice. Micro-computed tomography on day 21 showed a decreased tissue mineral density, a reduced bone volume and less trabeculae in the fracture callus indicating delayed fracture healing, probably due to the increased presence of inflammatory cells in TH CD11b-Cre mice. This indicates aFrontiers in Endocrinology frontiersin.org 01

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CCL2 is a critical mechano‐responsive mediator in crosstalk between osteoblasts and bone mesenchymal stromal cells

Cited by 12 publications

References 58 publications

Impact of the host response and osteoblast lineage cells on periodontal disease

Impact of the host response and osteoblast lineage cells on periodontal disease

Therapeutic Efficacy and Safety of Osteoinductive Factors and Cellular Therapies for Long Bone Fractures and Non-Unions: A Meta-Analysis and Systematic Review

Myeloid cell-derived catecholamines influence bone turnover and regeneration in mice

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