Osteocyte-Related Cytokines Regulate Osteoclast Formation and Bone Resorption

Kitaura, Hideki; Marahleh, Aseel; Ohori, Fumitoshi; Noguchi, Takahiro; Shen, Wei; Qi, Jiawei; Nara, Yasuhiko; Pramusita, Adya; Kinjo, Ria; Mizoguchi, Itaru

doi:10.3390/ijms21145169

Cited by 226 publications

(163 citation statements)

References 215 publications

(283 reference statements)

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“…The osteocyte population is a crucial regulator of both sclerostin and RANKL local expression during active periodontal disease (210). The sclerostin and RANKL are negative bone mass regulators by inhibiting Wnt signaling and by inducing osteoclastogenesis, respectively (210)(211)(212). Specifically, the receptor of RANKL, RANK, is expressed in the skeletal muscle tissue (213) and a deleterious effect of RANKL on muscle homeostasis has been suggested (212,214).…”

Section: Bone Conditions With Potential Muscle Implications In the Mamentioning

confidence: 99%

Muscle-Bone Crosstalk in the Masticatory System: From Biomechanical to Molecular Interactions

et al. 2021

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The masticatory system is a complex and highly organized group of structures, including craniofacial bones (maxillae and mandible), muscles, teeth, joints, and neurovascular elements. While the musculoskeletal structures of the head and neck are known to have a different embryonic origin, morphology, biomechanical demands, and biochemical characteristics than the trunk and limbs, their particular molecular basis and cell biology have been much less explored. In the last decade, the concept of muscle-bone crosstalk has emerged, comprising both the loads generated during muscle contraction and a biochemical component through soluble molecules. Bone cells embedded in the mineralized tissue respond to the biomechanical input by releasing molecular factors that impact the homeostasis of the attaching skeletal muscle. In the same way, muscle-derived factors act as soluble signals that modulate the remodeling process of the underlying bones. This concept of muscle-bone crosstalk at a molecular level is particularly interesting in the mandible, due to its tight anatomical relationship with one of the biggest and strongest masticatory muscles, the masseter. However, despite the close physical and physiological interaction of both tissues for proper functioning, this topic has been poorly addressed. Here we present one of the most detailed reviews of the literature to date regarding the biomechanical and biochemical interaction between muscles and bones of the masticatory system, both during development and in physiological or pathological remodeling processes. Evidence related to how masticatory function shapes the craniofacial bones is discussed, and a proposal presented that the masticatory muscles and craniofacial bones serve as secretory tissues. We furthermore discuss our current findings of myokines-release from masseter muscle in physiological conditions, during functional adaptation or pathology, and their putative role as bone-modulators in the craniofacial system. Finally, we address the physiological implications of the crosstalk between muscles and bones in the masticatory system, analyzing pathologies or clinical procedures in which the alteration of one of them affects the homeostasis of the other. Unveiling the mechanisms of muscle-bone crosstalk in the masticatory system opens broad possibilities for understanding and treating temporomandibular disorders, which severely impair the quality of life, with a high cost for diagnosis and management.

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Section: Bone Conditions With Potential Muscle Implications In the Mamentioning

confidence: 99%

Muscle-Bone Crosstalk in the Masticatory System: From Biomechanical to Molecular Interactions

et al. 2021

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“…Osteocytes, embedded within the bone matrix, are considered a type of endocrine cell which function to orchestrate the bone microenvironment via secretion of functional proteins targeting osteoclasts and osteoblasts ( 12 , 17 , 42 ). Significant induction of SASP components in irradiated osteocytes emphasizes their potential role in radiation-induced bone imbalances in remodeling.…”

Section: Resultsmentioning

confidence: 99%

“…It was previously reported that SASP triggers senescence of the surrounding normal cells ( 51 , 52 ). Many studies have focused on these secreted factors and their proposed mechanism in bone metabolism ( 12 , 53 ). IL-17A was found to mediate the promotion of osteoclastogenesis by osteocyte paracrine pathways ( 54 ), and MCP-1 has been indicated to play an important role in bone remodelling and bone-related cancers ( 55 ).…”

Section: Discussionmentioning

confidence: 99%

“…These results suggest that radiation-induced prematurely senescent osteocytes may produce and secrete SASP components, which in turn may regulate other cells in the surrounding medium, and may also activate macrophages. Osteocytes, embedded within the bone matrix, are considered a type of endocrine cell which function to orchestrate the bone microenvironment via secretion of functional proteins targeting osteoclasts and osteoblasts (12,17,42). Significant induction of SASP components in irradiated osteocytes emphasizes their potential role in radiation-induced bone imbalances in remodeling.…”

Section: Irradiation Induces Prematurely Senescent Osteocytes and Regmentioning

confidence: 99%

“…Osteocytes are the most abundant type of cells in the skeleton, are embedded within the mineralized bone matrix, and have long been deemed to be passive, metabolically inactive cells (8). However, studies have shown that osteocytes are multifunctional cells that both compose bone and respond to mechanical loads for weight support, and also exhibit key roles in bone remodeling and mineral homeostasis through secretory regulation of both osteoclasts and osteoblasts (9)(10)(11)(12). Targeting osteocytes and osteocyte-mediated pathways may hold promise in treating irradiation-related bone damage, therefore it is essential to investigate the effects of irradiation on osteocytes, and the underlying mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Radiation induces primary osteocyte senescence phenotype and affects osteoclastogenesis in vitro

Wang

et al. 2021

Int J Mol Med

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Irradiation-induced bone remodeling imbalances arise as a consequence of the dysregulation of bone formation and resorption. due to the abundance of osteocytes, their long life and their dual-regulatory effects on both osteoblast and osteoclast function, they serve as critical coordinators of bone remolding. In the present study, femur and tibia-derived primary osteocytes were cultured and irradiated to observe the functional changes and the cellular senescence phenotype in vitro. Irradiation directly reduced cell viability, affected the crucial dendritic morphology and altered the expression of functional proteins, including upregulation of receptor activator of nuclear factor-κB ligand and sclerostin, and downregulation of osteoprotegerin. Irradiated osteocytes were shown to exhibit notable dNA damage, which resulted in the initiation of a typical cellular senescence phenotype. Furthermore, it was found that irradiation-induced prematurely senescent osteocytes stimulate molecular secretion, referred to as senescence-associated secretory phenotype (SASP), which may be involved in modulation of the bone microenvironment, including the promotion of osteoclastogenesis. Taken together, the results showed that irradiation triggered osteocyte senescence and the acquisition of an associated secretory phenotype. This further resulted in an imbalance of bone remodeling through senescent influence on proliferation, morphology and marker protein production, but also indirectly via a paracrine pathway through SASP secretion. The results of the present study may highlight the potential of SASP-targeted interventions for the management of radiation-induced bone loss.

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Pathogenesis‐Guided Engineering of Multi‐Bioactive Hydrogel Co‐Delivering Inflammation‐Resolving Nanotherapy and Pro‐Osteogenic Protein for Bone Regeneration

Liu

Wang

et al. 2023

Adv Funct Materials

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There are still great challenges in promoting bone defect repair via regeneration strategies. In view of delayed bone healing due to local inflammation, herein, pathogenesis‐guided engineering of multi‐bioactive hydrogel therapy is proposed for bone regeneration, by simultaneously improving the osteoimmune environment and enhancing osteogenic differentiation of stem cells. After discovering the pivotal role of persistent inflammation and bone loss in the pathogenesis of periodontitis by transcriptomics, a multi‐bioactive nanotherapy based on self‐assembled nanomicelles (PP5 NMs) is first developed. PP5 NMs effectively rescue osteogenesis of human periodontal ligament cells under pathological conditions and promote bone formation in rats with mandibular or cranial bone defects. By integrating PP5 NMs, a pro‐osteogenic protein rhBMP9, and a hydrogel‐forming temperature‐responsive material, a multifunctional hydrogel therapy is further engineered, which can regulate the pro‐inflammatory/oxidative microenvironment and accelerate bone regeneration. The obtained multi‐bioactive hydrogel capable of co‐delivering and sustainedly releasing PP5 NMs and rhBMP9 displays excellent bone regeneration capability, by synergistic effects of inflammation‐resolving and pro‐osteogenic differentiation of stem cells. Mechanistically, this hydrogel therapy improves the osteoimmune environment by attenuating pathogenesis and enhancing stem cell differentiation via the TLR4/NF‐κB/HO‐1 axis and activating the Smad1/5/8 protein complex. The hydrogel is promising for treating different inflammatory bone diseases.

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Osteocyte-Related Cytokines Regulate Osteoclast Formation and Bone Resorption

Cited by 226 publications

References 215 publications

Muscle-Bone Crosstalk in the Masticatory System: From Biomechanical to Molecular Interactions

Muscle-Bone Crosstalk in the Masticatory System: From Biomechanical to Molecular Interactions

Radiation induces primary osteocyte senescence phenotype and affects osteoclastogenesis in vitro

Pathogenesis‐Guided Engineering of Multi‐Bioactive Hydrogel Co‐Delivering Inflammation‐Resolving Nanotherapy and Pro‐Osteogenic Protein for Bone Regeneration

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