Table 1 Piezo1 in bone development and homeostasis

From: Roles of mechanosensitive channel Piezo1/2 proteins in skeleton and other tissues

 

Cre

Development

Bone phenotype

Loading model

 

Embryo and Newborn

Young adult

Overall

Bone formation

Bone resorption

Loading model

Unloading model

MSC

Prx1-Cre30

P0: subtle difference

P3: increased cortical porosity in femurs

6 weeks: smaller long bones; indistinguishable calvariae; decreased cortical and trabecular bone mass and bone surface

Short long bones; significant trabecular bone mass loss; reduced cortical bone thickness and surface; reduced collagen expression

No significantly affected stem cells and progenitors; no difference for osteoblastogenesis; no difference of serum PINP

Increased osteoclast number and bone resorption activities: increased eroded surface, increased osteoclast number

Under FSS, WT BMSC-derived osteoblasts strongly increase Col2α1 and Col9α2 expression but not in Piezo1-deficient cells

HLU did not induce bone loss in cKO mice; increased TRAP-positive cells in WT but not in cKO mice

Prx1-Cre29

P0: multiple bone fractures in radius and ulna

3 weeks: short femurs

Short long bones; reduced cortical and trabecular bone mass

Reduced MAR, BFR; reduced osteoblast differentiation; reduced serum PINP; increase apoptosis in bone

Upregulated osteoclast differentiation: increased expression of osteoclast markers (Ctsk, TRAP)

n.a.

n.a.

Osteoblast lineage cell

Osx-Cre29

n.a.

3 weeks: multiple bone fractures in the ribs

Reduced trabecular and cortical bone mass

Reduced Osterix expression

n.a.

n.a.

n.a.

Runx2-Cre93

P1: no calvarial bone defects; no datable trabecular bone loss

P5: first rib fracture appears

2 weeks: multiple fractures in the ribs and femurs; shorter long bones.

12 weeks: pelvic dysplasia; reduced trabecular bone mass; no alteration of calvarial thickness or porosity

Enlarged hypertrophic zone at growth plate; remarkable reduction of trabecular bone mass below the growth plates

Moderate reduction in the mineral apposition rate at the trabecular bone surface; reduced serum P1NP and P1CP; altered flatten osteoblast morphology

Increased osteoclast number

n.a.

n.a.

Col2a1-Cre93

n.a.

12 weeks: pelvic dysplasia; modulation of reduced bone length

Reduced trabecular bone volume with most pronounced in the secondary spongiosa; no significant reduction of cortical thickness

Increased flattened osteoblasts

n.a.

n.a.

n.a.

Col1-CreERT30

n.a.

8-week aged mice, inject Tamoxifen for 2 weeks

Reduced trabecular bone mass and cortical thickness; compromised collagen expression

n.a.

Increased TRAP-positive osteoclasts

n.a.

n.a.

Ocn-Cre28

P0: similar skeletal size, incomplete of cranial closure

8 and 16 weeks: shorter stature, lower body weight; significant bone loss in both male and female.

Shorter long bones; reduced long bone strength; loss of bone mass.

Reduced bone formation rate; reduced osteoblastic marker gene expression (Col1a1, Ocn, Bglap); reduced serum Ocn and PINP.

Similar TRAP straining; no change of Nfact1/Acp5/Ctsk/Mmp9 mRNA level; no change of serum CTX-1

21 days’ treadmill exercise: no significant increase of osteoblast genes in cKO mice

28 days’ HLU: no further reduction of bone mass or bone strength in cKO mice

Dmp1-Cre27

Normal body weight

5, 8, and 12 weeks: normal body weight; low bone mineral density; difference increased as mice mature

Normal femur length; reduced trabecular bone mass and bone stiffness; spontaneous fractures in the tibia at 12 weeks

Reduced BFR; low osteoblast number; normal osteoblastogenesis; reduced Wnt1 mRNA in cortical bone; unaffected Sost expression in cortical bone

Increased osteoclast number; increased pro-osteoclastogenic cytokine RANKL but no changes for expression of OPG

14 days’ tibia loading: blunted load-stimulated bone formation in cKO mice

n.a.

Dmp1-Cre30

n.a.

n.a.

Decreased bone mass in both trabecular and cortical bones; no spontaneous fractures

n.a.

Increased osteoclast numbers

n.a.

n.a.

Dmp1-Cre93

n.a.

12 weeks: reduced trabecular and cortical bone mass

No significant changes in osteocyte number or the number of canalicular extensions

Altered trabecular osteoblasts with a flattened appearance in cKO mice

n.a.

Three consecutive days of ulna loading: reduced bone formation compared to control mice

n.a.

Osteoclasts

Ctsk-Cre30

n.a.

n.a.

Normal bone mass

n.a.

Unaffected bone resorption

n.a.

n.a.

Lyz2-Cre93

n.a.

12 weeks: no detectable skeletal phenotype

n.a.

n.a.

n.a.

n.a.

n.a.

  1. P postnatal, PINP aminoterminal propeptide of type I collagen, FSS fluid shear stress, WT Wield type, BMSC bone marrow stromal cell, Col collagen, HLU hind limb unloading, Ctsk Cathepsin K, TRAP tartrate-resistant acid phosphatase, cKO conditional knockout, MAR mineralization apposition rate, BFR bone formation rate, Ocn osteocalcin, Bglap bone gamma-carboxyglutamate protein, Nfact1 nuclear factor kB activator 1, Acp5 acid phosphatase 5, Mmp9 matrix metallopeptidase 9, CTX-1 crosslinked C-telopeptide of type I collagen, Wnt1 Wnt family member 1, Sost sclerostin, OPG osteoprotegerin, n.a. not applicable