Mechanisms of the Masquelet technique to promote bone defect repair and its influencing factors.

The Masquelet technique, also known as the induced membrane technique, is a surgical technique for repairing large bone defects based on the use of a membrane generated by a foreign body reaction for bone grafting. This technique is not only simple to perform, with few complications and quick recovery, but also has excellent clinical results. To better understand the mechanisms by which this technique promotes bone defect repair and the factors that require special attention in practice, we examined and summarized the relevant research advances in this technique by searching, reading, and analysing the literature. Literature show that the Masquelet technique may promote the repair of bone defects through the physical septum and molecular barrier, vascular network, enrichment of mesenchymal stem cells, and high expression of bone-related growth factors, and the repair process is affected by the properties of spacers, the timing of bone graft, mechanical environment, intramembrane filling materials, artificial membrane, and pharmaceutical/biological agents/physical stimulation.

Nitric Oxide Ameliorates the Effects of Hypoxia in Mice by Regulating Oxygen Transport by Hemoglobin.

Xiaoying Zhou, Wenting Su, Quanwei Bao, Yu Cui, Xiaoxu Li, Yidong Yang, Chengzhong Yang, Chengyuan Wang, Li Jiao, Dewei Chen, and Jian Huang. Nitric oxide ameliorates the effects of hypoxia in mice by regulating oxygen transport by hemoglobin. High Alt Med Biol. 00:00-00, 2024.-Hypoxia is a common pathological and physiological phenomenon in ischemia, cancer, and strenuous exercise. Nitric oxide (NO) acts as an endothelium-derived relaxing factor in hypoxic vasodilation and serves as an allosteric regulator of hemoglobin (Hb). However, the ultimate effects of NO on the hematological system in vivo remain unknown, especially in extreme environmental hypoxia. Whether NO regulation of the structure of Hb improves oxygen transport remains unclear. Hence, we examined whether NO altered the oxygen affinity of Hb (Hb-O2 affinity) to protect extremely hypoxic mice. Mice were exposed to severe hypoxia with various concentrations of NO, and the survival time, exercise capacity, and other physical indexes were recorded. The survival time was prolonged in the 5 ppm NO (6.09 ± 1.29 minutes) and 10 ppm NO (6.39 ± 1.58 minutes) groups compared with the 0 ppm group (4.98 ± 1.23 minutes). Hypoxia of the brain was relieved, and the exercise exhaustion time was prolonged when mice inhaled 20 ppm NO (24.70 ± 6.87 minutes vs. 20.23 ± 6.51 minutes). In addition, the differences in arterial oxygen saturation (SO2%) (49.64 ± 7.29% vs. 42.90 ± 4.30%) and arteriovenous SO2% difference (25.14 ± 8.95% vs. 18.10 ± 6.90%) obviously increased. In ex vivo experiments, the oxygen equilibrium curve (OEC) left shifted as P50 decreased from 43.77 ± 2.49 mmHg (0 ppm NO) to 40.97 ± 1.40 mmHg (100 ppm NO) and 38.36 ± 2.78 mmHg (200 ppm NO). Furthermore, the Bohr effect of Hb was enhanced by the introduction of 200 ppm NO (-0.72 ± 0.062 vs.-0.65 ± 0.051), possibly allowing Hb to more easily offload oxygen in tissue at lower pH. The crystal structure reveals a greater distance between Asp94ß-His146ß in nitrosyl -Hb(NO-Hb), NO-HbßCSO93, and S-NitrosoHb(SNO-Hb) compared to tense Hb(T-Hb, 3.7 Å, 4.3 Å, and 5.8 Å respectively, versus 3.5 Å for T-Hb). Moreover, hydrogen bonds were less likely to form, representing a key limitation of relaxed Hb (R-Hb). Upon NO interaction with Hb, hydrogen bonds and salt bridges were less favored, facilitating relaxation. We speculated that NO ameliorated the effects of hypoxia in mice by promoting erythrocyte oxygen loading in the lung and offloading in tissues.

Wnt/ß-catenin signalling promotes more effective fracture healing in aged mice than in adult mice by inducing angiogenesis and cell differentiation.

To investigate whether activating the Wnt/ß-catenin signalling pathway differentially promotes fracture healing in aged and adult individuals. CatnbTM2Kem, Catnblox(ex3) and wild-type adult and aged mice were used in this study. The femur was electroporated through a hole with a diameter of 0.6 mm. On the 7th, 14th and 21st days after fracture establishment, repair of the femoral diaphyseal bone was examined using X-ray and CT, the levels of mRNAs related to Wnt/ß-catenin signalling were detected using real-time polymerase chain reaction (RT-PCR), and angiogenesis and cell differentiation were observed using immunohistochemistry. The numbers of osteoclasts were determined by TRAP staining. Wnt/ß-catenin activation accelerated fracture healing in adult mice, with more pronounced effects on aged mice. Compared with wild-type mice at the corresponding ages, Wnt/ß-catenin signalling activation induced higher levels of angiogenesis and cell differentiation in aged mice than in adult mice and promoted fracture healing. The administration of medications targeting Wnt/ß-catenin signalling to aged patients may accelerate fracture healing to a greater extent.

First-aid Training for Combatants Without Systematic Medical Education Experience on the Battlefield: Establishment and Evaluation of the Curriculum in China.

INTRODUCTION: For combatants without systematic medical education experience (CSMEE), it is necessary to participate in first-aid on the battlefield, but currently there is no effective training curriculum for CSMEE in Chinese military. MATERIALS AND METHODS: A list of first-aid techniques based on expert consensus was formed, and then a curriculum was established according to the list. The effectiveness of the curriculum was further evaluated by comparing the scores among group A (the reserve officers trained by this curriculum), group B (the reserve officers in the military medical college trained by professional medic training system), and group C (the fresh officers trained by the Outline of Military Training and Assessment of Chinese military), through a 5-station assessment in a simulated battlefield environment, which included the following 5 techniques: tourniquet for massive extremities hemorrhage, thyrocricocentesis, thoracentesis, fixation of long bone fractures, and wound dressing with hemostatic bandage. RESULTS: The training curriculum entitled "Implementation and Assessment Standards of First-aid Training for Combatants on the Battlefield" was established. The comparison of average scores in the 5-station assessment showed that group A had better scores than group C in tourniquet for massive extremity hemorrhage, thyrocricocentesis, and thoracentesis, with no significant differences compared with group B. Also, no significant difference between groups A and B in overall completion time and overall scores was observed, whereas an excellent candidate rate in overall score of group B was better than that of group A (87.4% vs. 80.9%, χ2 = 4.40, p = 0.036), and group A was better than group C (80.9% vs. 37.5%, χ2 = 62.01, p < 0.001). CONCLUSION: The established training curriculum is indeed effective, which improved the CSMEE's first-aid capacity on the battlefield, and is equivalent to the level of medics.

The increase in bone resorption in early-stage type I diabetic mice is induced by RANKL secreted by increased bone marrow adipocytes.

Bone marrow adipose tissue (BMAT) has recently been found to induce osteoclastogenesis by secreting RANKL. Although Type 1 diabetes mellitus (T1DM) has been reported to be associated with increased BMAT and bone loss, little is known about the relationship between BMAT and osteoclasts in T1DM. We studied the role of BMAT in the alterations of osteoclast activities in early-stage T1DM, by using a streptozotocin-induced T1DM mouse model. Our results showed that osteoclast activity was enhanced in the long bones of T1DM mice, accompanied by increased protein expression of RANKL. However, RANKL mRNA levels in bone tissues of T1DM mice remained unchanged. Meanwhile, we found that BMAT was significantly increased in the long bones of T1DM mice, and both mRNA and protein levels of RANKL were elevated in the diabetic BMAT. More importantly, RANKL protein was mainly expressed on the cell membranes of the increased adipocytes, most of which were located next to the metaphyseal region. These results suggest that the enhanced bone resorption in early-stage diabetic mice is induced by RANKL derived from BMAT rather than the bone tissue itself.

Different effects of Wnt/ß-catenin activation and PTH activation in adult and aged male mice metaphyseal fracture healing.

BACKGROUND: Fractures in older men are not uncommon and need to be healed as soon as possible to avoid related complications. Anti-osteoporotic drugs targeting Wnt/ß-catenin and PTH (parathyroid hormone) to promote fracture healing have become an important direction in recent years. The study is to observe whether there is a difference in adult and aged situations by activating two signal paths. METHODS: A single cortical hole with a diameter of 0.6 mm was made in the femoral metaphysis of Catnblox(ex3) mice and wild-type mice. The fracture healing effects of CA (Wnt/ß-catenin activation) and PTH (activated by PTH (1-34) injections) were assessed by X-ray and CT imaging on days 7, 14, and 21 after fracture. The mRNA levels of ß-catenin, PTH1R(Parathyroid hormone 1 receptor), and RUNX2(Runt-related transcription factor 2) in the fracture defect area were detected using RT-PCR. Angiogenesis and osteoblasts were observed by immunohistochemistry and osteoclasts were observed by TRAP (Tartrate-resistant Acid Phosphatase). RESULT: Adult CA mice and adult PTH mice showed slightly better fracture healing than adult wild-type (WT) mice, but there was no statistical difference. Aged CA mice showed better promotion of angiogenesis and osteoblasts and better fracture healing than aged PTH mice. CONCLUSION: The application of Wnt/ß-catenin signaling pathway drugs for fracture healing in elderly patients may bring better early effects than PTH signaling pathway drugs, but the long-term effects need to be observed.

Preactivation of ß-catenin in osteoblasts improves the osteoanabolic effect of PTH in type 1 diabetic mice.

Type 1 diabetes (T1D) is correlated with osteopenia primarily due to low bone formation. Parathyroid hormone (PTH) is a known anabolic agent for bone, the anabolic effects of which are partially mediated through the Wnt/ß-catenin signaling pathway. In the present study, we first determined the utility of intermittent PTH treatment in a streptozotocin-induced T1D mouse model. It was shown that the PTH-induced anabolic effects on bone mass and bone formation were attenuated in T1D mice compared with nondiabetic mice. Further, PTH treatment failed to activate ß-catenin signaling in osteoblasts of T1D mice and was unable to improve osteoblast proliferation and differentiation. Next, the Col1-3.2 kb-CreERTM; ß-cateninfx(ex3) mice were used to conditionally activate ß-catenin in osteoblasts by injecting tamoxifen, and we addressed whether or not preactivation of ß-catenin boosted the anabolic action of PTH on T1D-related bone loss. The results demonstrated that pretreatment with activation of osteoblastic ß-catenin followed by PTH treatment outperformed PTH or ß-catenin activation monotherapy and led to greatly improved bone structure, bone mass, and bone strength in this preclinical model of T1DM. Further analysis demonstrated that osteoblast proliferation and differentiation, as well as osteoprogenitors in the marrow, were all improved in the combination treatment group. These findings indicated a clear advantage of developing ß-catenin as a target to improve the efficacy of PTH in the treatment of T1D-related osteopenia.

Efficacy of a Temporary Hemostatic Device in a Swine Model of Closed, Lethal Liver Injury.

INTRODUCTION: Solid abdominal organ hemorrhage remains one of the leading causes of death both on the battlefield of modern warfare and in the civilian setting. A novel, temporary hemostatic device combining CELOX and direct intra-abdominal physical compression was invented to control closed SAOH during transport to a medical treatment facility. MATERIALS AND METHODS: A swine model of closed, lethal liver injury was established to determine hemostasis. The animals were randomly divided into group A (extra-abdominal compression), group B (gauze packing), group C (intra-abdominal compression), group D (CELOX coverage), and group E (intra-abdominal compression and CELOX coverage) with six swines per group. Survival time (ST), blood loss (BL), vital signs, pathologic examination, and CT-scan were monitored to further observe the effectiveness of the device. RESULTS: Group E had an average 30-minute extension in ST (74.3 ± 15.4 minutes versus 44.0 ± 13.8 minutes, p = 0.026) with less BL (46.0 ± 13.0 versus 70.8 ± 8.2 g/kg, p = 0.018), and maintained mean arterial pressure≥70 mmHg and cardiac output ≥ 3.5 L/minute for a longer time. No significant differences were observed in ST and BL of groups B and E, and there were no marked differences in ST and BL of groups A, C, and D. No CELOX clots were noted in the spleen, pancreas, lungs, heart, kidneys, or the adjacent large vessels in groups D and E. Compared to group A, the CT-scan showed better hepatic hemorrhage control in group E. CONCLUSIONS: The device, which combined 20 g of CELOX particles and 20 pieces of CELOX (8 g) sponge tablets with 50-mmHg intra-abdominal compression for 10 minutes, prolonged the ST by an average of 30 minutes with less BL. It was not markedly different from the full four quadrants gauze packing of liver in hemostatic effect, with no CELOX clot formation in other organs.

Different effects of Wnt/ß-catenin activation and parathyroid hormone on diaphyseal and metaphyseal in the early phase of femur bone healing of mice.

Parathyroid hormone (PTH) and agents related to the manipulation of Wnt/ß-catenin signalling are two promising anabolic anti-osteoporotic therapies that have been shown to promote the healing of bone fractures. Now, it is widely accepted that cortical bone and trabecular bone are two different compartments, and should be treated as separate compartments in pathological processes, such as fracture healing. It is currently unknown whether PTH and the activation of ß-catenin signalling would demonstrate different effects on cortical bone and trabecular bone healing. In the current study, single 0.6-mm cortex holes were made in the femur metaphysis and diaphysis of mice, and then, PTH application and ß-catenin activation were used to observe the promoting effect on bone healing. The effects of ß-catenin and PTH signalling on fracture healing were observed by X-ray and CT at 3, 6, and 14 days after fracture, and the levels of ß-catenin were detected by RT-PCR assay, and the number of specific antigen-positive cells of BRDU, OCN, RUNX2 was counted by immunohistochemical staining. While ß-catenin activation and PTH were found to demonstrate similar effects on accelerating metaphyseal bone healing, activation of ß-catenin showed a more striking effect than PTH on promoting diaphyseal bone healing. These findings might be helpful for selecting proper medication to accelerate fracture healing of different bone compartments.

Differential effects of type 1 diabetes mellitus and subsequent osteoblastic ß-catenin activation on trabecular and cortical bone in a mouse model.

Type 1 diabetes mellitus (T1DM) is a pathological condition associated with osteopenia. WNT/ß-catenin signaling is implicated in this process. Trabecular and cortical bone respond differently to WNT/ß-catenin signaling in healthy mice. We investigated whether this signaling has different effects on trabecular and cortical bone in T1DM. We first established a streptozotocin-induced T1DM mouse model and then constitutively activated ß-catenin in osteoblasts in the setting of T1DM (T1-CA). The extent of bone loss was greater in trabecular bone than that in cortical bone in T1DM mice, and this difference was consistent with the reduction in the expression of ß-catenin signaling in the two bone compartments. Further experiments demonstrated that in T1DM mice, trabecular bone showed lower levels of insulin-like growth factor-1 receptor (IGF-1R) than the levels in cortical bone, leading to lower WNT/ß-catenin signaling activity through the inhibition of the IGF-1R/Akt/glycogen synthase kinase 3ß (GSK3ß) pathway. After ß-catenin was activated in T1-CA mice, the bone mass and bone strength increased to substantially greater extents in trabecular bone than those in cortical bone. In addition, the cortical bone of the T1-CA mice displayed an unexpected increase in bone porosity, with increased bone resorption. The downregulated expression of WNT16 might be responsible for these cortical bone changes. In conclusion, we found that although the activation of WNT/ß-catenin signaling increased the trabecular bone mass and bone strength in T1DM mice, it also increased the cortical bone porosity, impairing the bone strength. These findings should be considered in the future treatment of T1DM-related osteopenia.

Disruption of bone morphogenetic protein type IA receptor in osteoblasts impairs bone quality and bone strength in mice.

In recent years, several studies have found that the disruption of type IA receptor of bone morphogenetic proteins (BMPR1A) could increase bone mass. However, whether disruption of BMPR1A could have an effect on bone quality and bone strength is currently unknown. Osteoblast-targeted conditional knockout (cKO) of BMPRIA by crossing 3.2-kb Col1-CreER™ mice with BMPR1A fx +/+ mice was conducted. Then, in vitro and in vivo studies were employed to examine the effect of BMPR1A knockout on bone quality and bone strength. It was found that the ultimate force and stiffness of the femora decreased significantly in cKO mice when compared to control mice. The content of collagen and mineralization level decreased as the structure of the collagen became disorganized. The morphology of osteocytes in cKO mice was abnormal as well. The expression level of osteocalcin, a marker for the terminal differentiation of osteoblasts, decreased in cKO mice. This data indicated that the differentiation of osteoblasts in cKO mice was impaired. Immunohistochemistry examination revealed deregulated expression of dickkopf 1(DKK1) in osteocytes in cKO mice. Adding DKK1 to the culture medium reversed these effects. In conclusion, even though disruption of BMPR1A could increase bone mass, it also impairs bone quality and bone strength.

Expert consensus on the evaluation and diagnosis of combat injuries of the Chinese People's Liberation Army.

The accurate assessment and diagnosis of combat injuries are the basis for triage and treatment of combat casualties. A consensus on the assessment and diagnosis of combat injuries was made and discussed at the second annual meeting of the Professional Committee on Disaster Medicine of the Chinese People's Liberation Army (PLA). In this consensus agreement, the massive hemorrhage, airway, respiration, circulation and hypothermia (MARCH) algorithm, which is a simple triage and rapid treatment and field triage score, was recommended to assess combat casualties during the first-aid stage, whereas the abbreviated scoring method for combat casualty and the MARCH algorithm were recommended to assess combat casualties in level II facilities. In level III facilities, combined measures, including a history inquiry, thorough physical examination, laboratory examination, X-ray, and ultrasound examination, were recommended for the diagnosis of combat casualties. In addition, corresponding methods were recommended for the recognition of casualties needing massive transfusions, assessment of firearm wounds, evaluation of mangled extremities, and assessment of injury severity in this consensus.

An appropriate Wnt/ß-catenin expression level during the remodeling phase is required for improved bone fracture healing in mice.

Accumulating evidence demonstrates that the Wnt/ß-catenin signaling pathway plays a dominant role in bone repair. However, the role of Wnt/ß-catenin signaling in the remodeling phase during bone fracture healing is currently unknown. In the present study, ß-catenin was activated at different levels or deleted in mice at the late stage of fracture healing, and the effects on healing quality were investigated. Deletion of ß-catenin disturbed bone remodeling, as confirmed by increased bone resorption and decreased bone formation, and significantly decreased bone strength compared with wildtype mice. In addition, the constitutive activation of ß-catenin significantly increased the bone mass and delayed the bone remodeling process, resulting in slightly impaired bone strength. In contrast, a slight activation of ß-catenin significantly increased bone formation and slightly hindered bone resorption. These effects lead to improved bone fracture healing quality compared with wildtype mice. In summary, the present study provides the first demonstration showing that Wnt/ß-catenin signaling should be maintained at a slightly activated level during the late stage of fracture healing to ensure better bone fracture repair.

Different bone remodeling levels of trabecular and cortical bone in response to changes in Wnt/ß-catenin signaling in mice.

Trabecular bone and cortical bone have different bone remodeling levels, and the underlying mechanisms are not fully understood. In the present study, the expression of Wnt/ß-catenin signaling and its downstream molecules along with bone mass in trabecular and cortical bone were compared in wild-type mice, constitutive activation of ß-catenin (CA-ß-catenin) mice and ß-catenin deletion mice. It was found that the expression level of most of the examined genes such as Wnt3a, ß-catenin, osteocalcin and RANKL/OPG ratio were significantly higher in trabecular bone than in cortical bone in wild-type mice. CA-ß-catenin resulted in up-regulated expression of the above-mentioned genes except for RANKL/OPG ratio, which were down-regulated. Also, CA-ß-catenin led to increased number of osteoblasts, decreased number of osteoclasts and increased bone mass in both the trabecular bone and cortical bone compared with wild-type mice; however, the extent of changes was much greater in the trabecular bone than in the cortical bone. By contrast, null ß-catenin led to down-regulated expression of the above-mentioned genes except for RANKL/OPG ratio. Furthermore, ß-catenin deletion led to decreased number of osteoblasts, increased number of osteoclasts and decreased bone mass when compared with wild-type mice. Again, the extent of these changes was more significant in trabecular bone than cortical bone. Taken together, we found that the expression level of Wnt/ß-catenin signaling and bone remodeling-related molecules were different in cortical bone and trabecular bone, and the trabecular bone was more readily affected by changes in the Wnt/ß-catenin signaling pathway. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:812-819, 2017.

Constitutive ß-catenin activation in osteoblasts impairs terminal osteoblast differentiation and bone quality.

Accumulating evidence suggests that Wnt/ß-catenin signaling plays a central role in controlling bone mass. We previously reported that constitutive activation of ß-catenin (CA-ß-catenin) in osteoblasts potentially has side effects on the bone growth and bone remodeling process, although it could increase bone mass. The present study aimed to observe the effects of osteoblastic CA-ß-catenin on bone quality and to investigate possible mechanisms of these effects. It was found that CA-ß-catenin mice exhibited lower mineralization levels and disorganized collagen in long bones as confirmed by von Kossa staining and sirius red staining, respectively. Also, bone strength decreased significantly in CA-ß-catenin mice. Then the effect of CA-ß-catenin on biological functions of osteoblasts were investigated and it was found that the expression levels of osteocalcin, a marker for the late differentiation of osteoblasts, decreased in CA-ß-catenin mice, while the expression levels of osterix and alkaline phosphatase, two markers for the early differentiation of osteoblasts, increased in CA-ß-catenin mice. Furthermore, higher proliferation rate were revealed in osteoblasts that were isolated from CA-ß-catenin mice. The Real-time PCR and western blot examination found that the expression level of c-myc and cyclin D1, two G1 progression-related molecules, increased in osteoblasts that were isolated from the CA-ß-catenin mice, and the expression levels of CDK14 and cyclin Y, two mitotic-related molecules that can accelerate cells entering into S and G2/M phases, increased in osteoblasts that were isolated from the CA-ß-catenin mice. In summary, osteoblastic CA-ß-catenin kept osteoblasts in high proliferative state and impaired the terminal osteoblast differentiation, and this led to changed bone structure and decreased bone strength.

Diagnosis and treatment of rare complications of pelvic fractures.

PURPOSE: To enhance the awareness of rare complications of pelvic fracture and describe the correct diagnosis and effective treatment. METHODS: A total of 188 cases of pelvic fractures were retrospectively reviewed, and four patients who suffered from four types of rare pelvic fracture complications were described, namely ureteral obstruction caused by retroperitoneal hematoma-induced abdominal compartment syndrome (ACS), bowel entrapment, external iliac artery injury, and open scrotal sac injury. RESULTS: We demonstrated that combined measures should be employed to prevent the occurrence of ACS following major pelvic fractures. Ureteral catheter support may be a good option at an early stage when ACS occurred. Contrasted computed tomography examination and sufficient awareness are keys to a correct diagnosis of bowel entrapment following pelvic fractures. Recognition of risk factors, early diagnosis, and prompt treatment of suspected injury of the external iliac artery are keys to patient survival and to avoid limb loss. Scrotal and/or testicular injury complicated by pelvic fractures should be carefully treated to maintain normal gonad function. Additionally, establishment of a sophisticated trauma care system and multi-disciplinary coordination are important for correct diagnosis and treat- ment of rare complications in pelvic fractures. CONCLUSIONS: Rare complications of pelvic fractures are difficult to diagnose and negatively impact outcome. Recognition of risk factors and sufficient awareness are essential for correct diagnosis and prompt treatment.

Adverse Effects of Osteocytic Constitutive Activation of ß-Catenin on Bone Strength and Bone Growth.

The activation of the canonical Wnt/ß-catenin signaling pathway in both mesenchymal stem cells and osteoblasts has been demonstrated to increase bone mass, showing promise for the treatment of low bone volume conditions such as osteoporosis. However, the possible side effects of manipulating this pathway have not been fully addressed. Previously, we reported that the constitutive activation of ß-catenin in osteoblasts impaired vertebral linear growth. In the present study, ß-catenin was constitutively activated in osteocytes by crossing Catnb+/lox(exon 3) mice with dentin matrix protein 1(DMP1)-Cre transgenic mice, and the effects of this activation on bone mass, bone growth and bone strength were then observed. DMP1-Cre was found to be predominantly expressed in osteocytes, with weak expression in a small portion of osteoblasts and growth plate chondrocytes. After the activation, the cancellous bone mass was dramatically increased, almost filling the entire bone marrow cavity in long bones. However, bone strength decreased significantly. Thinner and more porous cortical bone along with impaired mineralization were responsible for the decrease in bone strength. Furthermore, the mice showed shorter stature with impaired linear growth of the long bones. Moreover, the concentration of serum phosphate decreased significantly after the activation of ß-catenin, and a high inorganic phosphate (Pi) diet could partially rescue the phenotype of decreased mineralization level and impaired linear growth. Taken together, the constitutive activation of ß-catenin in osteocytes may increase cancellous bone mass; however, the activation also had adverse effects on bone strength and bone growth. These adverse effects should be addressed before the adoption of any therapeutic clinical application involving adjustment of the Wnt/ß-catenin signaling pathway.