Wnt Pathway in Bone Repair and Regeneration – What Do We Know So Far

Abstract

Wnt signaling plays a central regulatory role across a remarkably diverse range of functions during embryonic development, including those involved in the formation of bone and cartilage. Wnt signaling continues to play a critical role in adult osteogenic differentiation of mesenchymal stem cells. Disruptions in this highly-conserved and complex system leads to various pathological conditions, including impaired bone healing, autoimmune diseases and malignant degeneration. For reconstructive surgeons, critically sized skeletal defects represent a major challenge. These are frequently associated with significant morbidity in both the recipient and donor sites. The Wnt pathway is an attractive therapeutic target with the potential to directly modulate stem cells responsible for skeletal tissue regeneration and promote bone growth, suggesting that Wnt factors could be used to promote bone healing after trauma. This review summarizes our current understanding of the essential role of the Wnt pathway in bone regeneration and repair.

Wnt3a and wnt5a as Potential Chondrogenic Stimulators for Nucleus Pulposus Cell Induction: A Comprehensive Review

“…52 However, this phenomenon has not been studied in human NP cells. Studies conducted on human cells primarily focus on the canonical pathway, 53 in which contradictive results are obtained as specific downregulation of wnt/β-catenin signaling leads to NP cell apoptosis, 54 while activation of wnt/β-catenin signaling is also reported to result in NP cell apoptosis. 55 Canonical and noncanonical signaling appears to have crosstalk leading to a chain of reactions which are likely challenging to control.…”

Wnt-Signalwege bei kutaner Wundheilung

“…In diesem Zusammenhang wird dem Wnt-Signalweg eine bedeutende Rolle bei der Organentwicklung, in der Embryogenese, der Krebsentstehung sowie der Zell-Determination zugeschrieben [17]. Beim Menschen gibt es derzeit 19 charakterisierte Wnt-Proteine und zehn verschiedene Frizzled-Rezeptoren [18]. Der Wnt-Signalweg lässt sich in Abhängigkeit von β-Catenin bei der Signaltransduktion in drei grundlegende Wege unterteilen [18]: Der kanonische, β-Catenin-abhängige Signalweg, ist der am besten untersuchte Wnt-Weg.…”

“…Beim Menschen gibt es derzeit 19 charakterisierte Wnt-Proteine und zehn verschiedene Frizzled-Rezeptoren [18]. Der Wnt-Signalweg lässt sich in Abhängigkeit von β-Catenin bei der Signaltransduktion in drei grundlegende Wege unterteilen [18]: Der kanonische, β-Catenin-abhängige Signalweg, ist der am besten untersuchte Wnt-Weg. Zudem sind zwei nicht-kanonische, β-Catenin-unabhängige Signalkaskaden bekannt, zu denen der planar cell polarity (PCR)-Signalweg und der Wnt/Calcium-Signalweg gehören.…”

Prioritization of osteoporosis-associated GWAS SNPs using epigenomics and transcriptomics

“…Three of these, BICC1, LGR4, DAAM2, are involved directly or indirectly in canonical Wnt signaling, a signaling pathway that plays critical roles in osteoblastogenesis and bone homeostasis. (46)(47)(48) The other two genes are NPR3, and HMGA2, a mediator of natriuretic signaling and an essential component of enhanceosomes, respectively. (28,49) One of the most interesting genes for which we identified novel regulatory candidate SNPs is BICC1, which encodes a self-polymerizing RNA-binding protein that indirectly regulates Wnt signaling.…”