From Translation to Protein Degradation as Mechanisms for Regulating Biological Functions: A Review on the SLRP Family in Skeletal Tissues

Zappia, Jérémie; Joiret, Marc; Sanchez, Christelle; Lambert, Cécile; Geris, Liesbet; Müller, Marc; Henrotin, Yves

doi:10.3390/biom10010080

Cited by 16 publications

(22 citation statements)

References 170 publications

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“…Majority of ECM components are the proteoglycans, among which the SLRPs are the largest family 31 . SLRPs are capable of clustering different types of receptors and affecting downstream intracellular phosphorylation events, including those driven by TGF-beta/BMP superfamily members, epidermal growth factor receptors, insulin like growth factor I receptors, Met receptor and Toll-like receptors 32 , 33 .…”

Section: Discussionmentioning

confidence: 99%

Osteomodulin positively regulates osteogenesis through interaction with BMP2

et al. 2021

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Osteomodulin (OMD), a member of the small leucine-rich proteoglycan family, distributes in mineralized tissues and is positively regulated by bone morphogenetic protein 2 (BMP2). However, the exact function of OMD during mineralization and its association with BMP2 remain poorly understood. Herein, the expression pattern of OMD during osteogenesis was investigated in human dental pulp stem cells. Silencing OMD gene significantly suppressed the alkaline phosphatase activity, mineralized nodule formation and osteogenesis-associated gene transcription. Besides, OMD could enhance BMP2-induced expression of SP7 and RUNX2 with concentration dependence in vitro. Rat mandibular bone defect model revealed that scaffolds injected with the combination of OMD and suboptimal BMP2 exhibited more mature and abundant mineralized bone than that treated with OMD or suboptimal BMP2 alone. Mechanistically, OMD could bind to BMP2 via its terminal leucine-rich repeats and formed complexes with BMP2 and its membrane receptors, thus promoting BMP/SMAD signal transduction. In addition, OMD was a putative target gene of SMAD4, which plays a pivotal role in this pathway. Collectively, these data elucidate that OMD may act as a positive coordinator in osteogenesis through BMP2/SMADs signaling.

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Section: Discussionmentioning

confidence: 99%

Osteomodulin positively regulates osteogenesis through interaction with BMP2

et al. 2021

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“…Decorin, biglycan, fibromodulin, lumican, PRELP (proline-arginine-rich-end-leucine-rich repeat protein), chondroadherin, and osteoadherin are members of the small leucine-rich repeat protein (SLRP) family, as reviewed by Zappia et al ( 31 ). Fibromodulin is a keratan sulfate proteoglycan found in cartilage and tendon.…”

Section: Extracellular Damage-associated Molecular Patterns From Cartmentioning

confidence: 99%

The Damage-Associated Molecular Patterns (DAMPs) as Potential Targets to Treat Osteoarthritis: Perspectives From a Review of the Literature

et al. 2021

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During the osteoarthritis (OA) process, activation of immune systems, whether innate or adaptive, is strongly associated with low-grade systemic inflammation. This process is initiated and driven in the synovial membrane, especially by synovium cells, themselves previously activated by damage-associated molecular patterns (DAMPs) released during cartilage degradation. These fragments exert their biological activities through pattern recognition receptors (PRRs) that, as a consequence, induce the activation of signaling pathways and beyond the release of inflammatory mediators, the latter contributing to the vicious cycle between cartilage and synovial membrane. The primary endpoint of this review is to provide the reader with an overview of these many molecules categorized as DAMPs and the contribution of the latter to the pathophysiology of OA. We will also discuss the different strategies to control their effects. We are convinced that a better understanding of DAMPs, their receptors, and associated pathological mechanisms represents a decisive issue for degenerative joint diseases such as OA.

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“…Although lumican belongs to the SLRP family and may therefore be involved in bone metabolism [5], the effects of lumican on bone biology are not yet fully understood. In vitro and animal experiments have demonstrated that lumican promotes preosteoblast viability and differentiation via integrin α2β1 and downstream ERK signaling, leading to bone formation [14].…”

Section: Inhibition Of In Vitro Bone Resorption and Osteoclastogenesis By Lumican Treatmentmentioning

confidence: 99%

“…SLRPs directly or indirectly regulate multiple cellular processes through interactions with various growth factors, cytokines, cell surface receptors, and other ECM components [ 4 ]. Importantly, most SLRPs are enriched in skeletal tissues [ 5 ], and several lines of evidence indicate that specific SLRPs play critical roles in bone homeostasis [ 6 , 7 ]. For example, mice lacking biglycan, a class I SLRP, exhibit osteoporotic phenotypes caused by a reduction in new bone formation and an increase in osteoclastogenesis [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…The ubiquitously expressed protein lumican, originally identified as a major component of the cornea [ 11 ], has been utilized in a wide range of biological functions including cell proliferation, differentiation, migration, and adhesion, in a variety of tissues [ 12 , 13 ]. Although lumican belongs to the SLRP family and may therefore be involved in bone metabolism [ 5 ], the effects of lumican on bone biology are not yet fully understood. In vitro and animal experiments have demonstrated that lumican promotes preosteoblast viability and differentiation via integrin α2β1 and downstream ERK signaling, leading to bone formation [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity

Lee

Kim

et al. 2021

IJMS

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Lumican, a ubiquitously expressed small leucine-rich proteoglycan, has been utilized in diverse biological functions. Recent experiments demonstrated that lumican stimulates preosteoblast viability and differentiation, leading to bone formation. To further understand the role of lumican in bone metabolism, we investigated its effects on osteoclast biology. Lumican inhibited both osteoclast differentiation and in vitro bone resorption in a dose-dependent manner. Consistent with this, lumican markedly decreased the expression of osteoclastogenesis markers. Moreover, the migration and fusion of preosteoclasts and the resorptive activity per osteoclast were significantly reduced in the presence of lumican, indicating that this protein affects most stages of osteoclastogenesis. Among RANKL-dependent pathways, lumican inhibited Akt but not MAP kinases such as JNK, p38, and ERK. Importantly, co-treatment with an Akt activator almost completely reversed the effect of lumican on osteoclast differentiation. Taken together, our findings revealed that lumican inhibits osteoclastogenesis by suppressing Akt activity. Thus, lumican plays an osteoprotective role by simultaneously increasing bone formation and decreasing bone resorption, suggesting that it represents a dual-action therapeutic target for osteoporosis.

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From Translation to Protein Degradation as Mechanisms for Regulating Biological Functions: A Review on the SLRP Family in Skeletal Tissues

Cited by 16 publications

References 170 publications

Osteomodulin positively regulates osteogenesis through interaction with BMP2

Osteomodulin positively regulates osteogenesis through interaction with BMP2

The Damage-Associated Molecular Patterns (DAMPs) as Potential Targets to Treat Osteoarthritis: Perspectives From a Review of the Literature

Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity

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