Sfrp4 is required to maintain Ctsk-lineage periosteal stem cell niche function

Chen, Ruiying; Dong, Han; Raval, Dhairya; Maridas, David; Baroi, Sudipta; Chen, Kun; Hu, Dorothy; Berry, Shawn R.; Baron, Roland; Greenblatt, Matthew B.; Gori, Francesca

doi:10.1073/pnas.2312677120

Cited by 3 publications

(1 citation statement)

References 86 publications

(160 reference statements)

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“…There are still a lot of uncertainties about these two bone healing pathways. Aided by Cre-based lineage trace, cells marked by expression of CtsK [60], periostin [7], αSMA [30,33], Axin2 [38], and Sox9 [36,37] were found in periosteum. Once again, they proved that PDSCs/PDPCs mainly contribute to fracture callus formation.…”

Section: The Dominant Role Of Periosteum In Fracture Healingmentioning

confidence: 99%

Periosteum Containing Implicit Stem Cells: A Progressive Source of Inspiration for Bone Tissue Regeneration

Zhang,

Deng,

2024

IJMS

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The periosteum is known as the thin connective tissue covering most bone surfaces. Its extrusive bone regeneration capacity was confirmed from the very first century-old studies. Recently, pluripotent stem cells in the periosteum with unique physiological properties were unveiled. Existing in dynamic contexts and regulated by complex molecular networks, periosteal stem cells emerge as having strong capabilities of proliferation and multipotential differentiation. Through continuous exploration of studies, we are now starting to acquire more insight into the great potential of the periosteum in bone formation and repair in situ or ectopically. It is undeniable that the periosteum is developing further into a more promising strategy to be harnessed in bone tissue regeneration. Here, we summarized the development and structure of the periosteum, cell markers, and the biological features of periosteal stem cells. Then, we reviewed their pivotal role in bone repair and the underlying molecular regulation. The understanding of periosteum-related cellular and molecular content will help enhance future research efforts and application transformation of the periosteum.

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Section: The Dominant Role Of Periosteum In Fracture Healingmentioning

confidence: 99%

Periosteum Containing Implicit Stem Cells: A Progressive Source of Inspiration for Bone Tissue Regeneration

Zhang,

Deng,

2024

IJMS

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β-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture

Huang,

Wu,

Jiang

et al. 2024

Bone Res

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The autonomic nervous system plays a crucial role in regulating bone metabolism, with sympathetic activation stimulating bone resorption and inhibiting bone formation. We found that fractures lead to increased sympathetic tone, enhanced osteoclast resorption, decreased osteoblast formation, and thus hastened systemic bone loss in ovariectomized (OVX) mice. However, the combined administration of parathyroid hormone (PTH) and the β-receptor blocker propranolol dramatically promoted systemic bone formation and osteoporotic fracture healing in OVX mice. The effect of this treatment is superior to that of treatment with PTH or propranolol alone. In vitro, the sympathetic neurotransmitter norepinephrine (NE) suppressed PTH-induced osteoblast differentiation and mineralization, which was rescued by propranolol. Moreover, NE decreased the PTH-induced expression of Runx2 but enhanced the expression of Rankl and the effect of PTH-stimulated osteoblasts on osteoclastic differentiation, whereas these effects were reversed by propranolol. Furthermore, PTH increased the expression of the circadian clock gene Bmal1, which was inhibited by NE-βAR signaling. Bmal1 knockdown blocked the rescue effect of propranolol on the NE-induced decrease in PTH-stimulated osteoblast differentiation. Taken together, these results suggest that propranolol enhances the anabolic effect of PTH in preventing systemic bone loss following osteoporotic fracture by blocking the negative effects of sympathetic signaling on PTH anabolism.

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Sfrp4 is required to maintain Ctsk-lineage periosteal stem cell niche function

Chen,

Dong,

Raval

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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We have previously reported that the cortical bone thinning seen in mice lacking the Wnt signaling antagonistSfrp4is due in part to impaired periosteal apposition. The periosteum contains cells which function as a reservoir of stem cells and contribute to cortical bone expansion, homeostasis, and repair. However, the local or paracrine factors that govern stem cells within the periosteal niche remain elusive. Cathepsin K (Ctsk), together with additional stem cell surface markers, marks a subset of periosteal stem cells (PSCs) which possess self-renewal ability and inducible multipotency.Sfrp4is expressed in periosteal Ctsk-lineage cells, andSfrp4global deletion decreases the pool of PSCs, impairs their clonal multipotency for differentiation into osteoblasts and chondrocytes and formation of bone organoids. Bulk RNA sequencing analysis of Ctsk-lineage PSCs demonstrated thatSfrp4deletion down-regulates signaling pathways associated with skeletal development, positive regulation of bone mineralization, and wound healing. Supporting these findings,Sfrp4deletion hampers the periosteal response to bone injury and impairs Ctsk-lineage periosteal cell recruitment. Ctsk-lineage PSCs express the PTH receptor and PTH treatment increases the % of PSCs, a response not seen in the absence ofSfrp4. Importantly, in the absence ofSfrp4, PTH-dependent increase in cortical thickness and periosteal bone formation is markedly impaired. Thus, this study provides insights into the regulation of a specific population of periosteal cells by a secreted local factor, and shows a central role for Sfrp4 in the regulation of Ctsk-lineage periosteal stem cell differentiation and function.

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Sfrp4 is required to maintain Ctsk-lineage periosteal stem cell niche function

Cited by 3 publications

References 86 publications

Periosteum Containing Implicit Stem Cells: A Progressive Source of Inspiration for Bone Tissue Regeneration

Periosteum Containing Implicit Stem Cells: A Progressive Source of Inspiration for Bone Tissue Regeneration

β-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture

Sfrp4 is required to maintain Ctsk-lineage periosteal stem cell niche function

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