Table 1 Piezo1 in bone development and homeostasis
From: Roles of mechanosensitive channel Piezo1/2 proteins in skeleton and other tissues
| Â | Cre | Development | Bone phenotype | Loading model | ||||
|---|---|---|---|---|---|---|---|---|
| Â | 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. | |