Two Modulators of Skeletal Development: BMPs and Proteoglycans
During embryogenesis, skeletal development is tightly regulated by locally secreted growth factors that interact with proteoglycans (PGs) in the extracellular matrix (ECM). Bone morphogenetic proteins (BMPs) are multifunctional growth factors that play critical roles in cartilage maturation and bone...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Journal of Developmental Biology |
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| Online Access: | https://www.mdpi.com/2221-3759/10/2/15 |
| _version_ | 1797485914005438464 |
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| author | Elham Koosha B. Frank Eames |
| author_facet | Elham Koosha B. Frank Eames |
| author_sort | Elham Koosha |
| collection | DOAJ |
| description | During embryogenesis, skeletal development is tightly regulated by locally secreted growth factors that interact with proteoglycans (PGs) in the extracellular matrix (ECM). Bone morphogenetic proteins (BMPs) are multifunctional growth factors that play critical roles in cartilage maturation and bone formation. BMP signals are transduced from plasma membrane receptors to the nucleus through both canonical Smad and noncanonical p38 mitogen-activated protein kinase (MAPK) pathways. BMP signalling is modulated by a variety of endogenous and exogenous molecular mechanisms at different spatiotemporal levels and in both positive and negative manners. As an endogenous example, BMPs undergo extracellular regulation by PGs, which generally regulate the efficiency of ligand-receptor binding. BMP signalling can also be exogenously perturbed by a group of small molecule antagonists, such as dorsomorphin and its derivatives, that selectively bind to and inhibit the intracellular kinase domain of BMP type I receptors. In this review, we present a current understanding of BMPs and PGs functions in cartilage maturation and osteoblast differentiation, highlighting BMP–PG interactions. We also discuss the identification of highly selective small-molecule BMP receptor type I inhibitors. This review aims to shed light on the importance of BMP signalling and PGs in cartilage maturation and bone formation. |
| first_indexed | 2024-03-09T23:25:38Z |
| format | Article |
| id | doaj.art-b499db3be8b649c5992224a9a0a907b6 |
| institution | Directory Open Access Journal |
| issn | 2221-3759 |
| language | English |
| last_indexed | 2024-03-09T23:25:38Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Developmental Biology |
| spelling | doaj.art-b499db3be8b649c5992224a9a0a907b62023-11-23T17:18:50ZengMDPI AGJournal of Developmental Biology2221-37592022-04-011021510.3390/jdb10020015Two Modulators of Skeletal Development: BMPs and ProteoglycansElham Koosha0B. Frank Eames1Department of Anatomy, Physiology and Pharmacology (APP), College of Medicine, University of Saskatchewan, 2D01-107 Wiggins Road, Saskatoon, SK S7N 5E5, CanadaDepartment of Anatomy, Physiology and Pharmacology (APP), College of Medicine, University of Saskatchewan, 2D01-107 Wiggins Road, Saskatoon, SK S7N 5E5, CanadaDuring embryogenesis, skeletal development is tightly regulated by locally secreted growth factors that interact with proteoglycans (PGs) in the extracellular matrix (ECM). Bone morphogenetic proteins (BMPs) are multifunctional growth factors that play critical roles in cartilage maturation and bone formation. BMP signals are transduced from plasma membrane receptors to the nucleus through both canonical Smad and noncanonical p38 mitogen-activated protein kinase (MAPK) pathways. BMP signalling is modulated by a variety of endogenous and exogenous molecular mechanisms at different spatiotemporal levels and in both positive and negative manners. As an endogenous example, BMPs undergo extracellular regulation by PGs, which generally regulate the efficiency of ligand-receptor binding. BMP signalling can also be exogenously perturbed by a group of small molecule antagonists, such as dorsomorphin and its derivatives, that selectively bind to and inhibit the intracellular kinase domain of BMP type I receptors. In this review, we present a current understanding of BMPs and PGs functions in cartilage maturation and osteoblast differentiation, highlighting BMP–PG interactions. We also discuss the identification of highly selective small-molecule BMP receptor type I inhibitors. This review aims to shed light on the importance of BMP signalling and PGs in cartilage maturation and bone formation.https://www.mdpi.com/2221-3759/10/2/15proteoglycansBMPscartilage maturationosteoblast differentiation |
| spellingShingle | Elham Koosha B. Frank Eames Two Modulators of Skeletal Development: BMPs and Proteoglycans Journal of Developmental Biology proteoglycans BMPs cartilage maturation osteoblast differentiation |
| title | Two Modulators of Skeletal Development: BMPs and Proteoglycans |
| title_full | Two Modulators of Skeletal Development: BMPs and Proteoglycans |
| title_fullStr | Two Modulators of Skeletal Development: BMPs and Proteoglycans |
| title_full_unstemmed | Two Modulators of Skeletal Development: BMPs and Proteoglycans |
| title_short | Two Modulators of Skeletal Development: BMPs and Proteoglycans |
| title_sort | two modulators of skeletal development bmps and proteoglycans |
| topic | proteoglycans BMPs cartilage maturation osteoblast differentiation |
| url | https://www.mdpi.com/2221-3759/10/2/15 |
| work_keys_str_mv | AT elhamkoosha twomodulatorsofskeletaldevelopmentbmpsandproteoglycans AT bfrankeames twomodulatorsofskeletaldevelopmentbmpsandproteoglycans |