Local inhibition of 5-lipoxygenase enhances bone formation in a rat model

Cottrell, Jessica; Keshav, V.; Mitchell, Ashley; O’Connor, J. P.

doi:10.1302/2046-3758.22.2000066

Cited by 15 publications

(8 citation statements)

References 45 publications

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“…Fracture healing in long-term COX2 deficiency was demonstrated to be impaired [47]. In contrast, reduction of 5-LOX is associated with enhanced fracture healing, including elevated callus chondrogenesis and osteogenesis [11, 48, 49]. Somjen et al showed that baicalein blocks parathormone (PTH)-induced DNA synthesis unless 12- and 15-lipoxygenase are added [50].…”

Section: Discussionmentioning

confidence: 99%

“…The increased expression of bone resorption markers such as Trap and Rankl as well as Il-7 may explain the phenomenon of reduced early callus formation. However, the finding that 5-lipoxygenase knockout mice developed a callus rapidly and the bone healed faster [11, 48] contradicts this theory and could indicate that the inhibition of 5-LOX is not the only pathway through which baicalein manipulates bone healing. The inhibition of NF-κB by baicalein can have serious adverse effects through the whole bone-healing process [65].…”

Section: Discussionmentioning

confidence: 99%

“…Recent promising therapeutic approaches include lipoxygenase (LOX) inhibitors, which were found to ameliorate bone density [9]. The subgroup of 5-lipoxygenase (5-LOX) inhibitors were found to inhibit osteoclast formation [10] and enhance bone formation [11]. One of these lipoxygenase inhibitors is baicalein, a phytochemical agent extracted from the plant Scutellaria baicalensis Georg.…”

Section: Introductionmentioning

confidence: 99%

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Effect of the lipoxygenase inhibitor baicalein on bone tissue and bone healing in ovariectomized rats

Saul¹,

Weber²,

Zimmermann³

et al. 2019

Nutr Metab (Lond)

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BackgroundOsteoporosis is one of the world’s major medical burdens in the twenty-first century. Pharmaceutical intervention currently focusses on decelerating bone loss, but phytochemicals such as baicalein, which is a lipoxygenase inhibitor, may rescue bone loss. Studies evaluating the effect of baicalein in vivo are rare.MethodsWe administered baicalein to sixty-one three-month-old female Sprague-Dawley rats. They were divided into five groups, four of which were ovariectomized (OVX) and one non-ovariectomized (NON-OVX). Eight weeks after ovariectomy, bilateral tibial osteotomy with plate osteosynthesis was performed and bone formation quantified. Baicalein was administered subcutaneously using three doses (C1: 1 mg/kg BW; C2: 10 mg/kg BW; and C3: 100 mg/kg BW) eight weeks after ovariectomy for four weeks. Finally, femora and tibiae were collected. Biomechanical tests, micro-CT, ashing, histological and gene expression analyses were performed.ResultsBiomechanical properties were unchanged in tibiae and reduced in femora. In tibiae, C1 treatment enhanced callus density and cortical width and decreased callus area. In the C3 group, callus formation was reduced during the first 3 weeks after osteotomy, correlating to a higher mRNA expression of Osteocalcin, Tartrate-resistant acid phosphatase and Rankl. In femora, baicalein treatments did not alter bone parameters.ConclusionsBaicalein enhanced callus density and cortical width but impaired early callus formation in tibiae. In femora, it diminished the biomechanical properties and calcium-to-phosphate ratio. Thus, it is not advisable to apply baicalein to treat early bone fractures. To determine the exact effects on bone healing, further studies in which baicalein treatments are started at different stages of healing are needed.Electronic supplementary materialThe online version of this article (10.1186/s12986-018-0327-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of the lipoxygenase inhibitor baicalein on bone tissue and bone healing in ovariectomized rats

Saul¹,

Weber²,

Zimmermann³

et al. 2019

Nutr Metab (Lond)

View full text Add to dashboard Cite

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“…Furthermore, 5‐LO has been considered a key mediator of RANKL‐induced osteoclast formation (Lee et al., ; Moura et al., ). Other studies have also shown that the inhibition of 5‐LO is associated with increased bone formation (Cottrell, Keshav, Mitchell, & O'Connor, ; Gallwitz et al., ; Manigrasso & O'Connor, ). Therefore, the results presented herein show that the absence of 5‐LO decreased recruitment and differentiation of osteoclast precursors after Aa infection and consequently impaired alveolar bone loss.…”

Section: Discussionmentioning

confidence: 91%

The role of 5‐lipoxygenase in Aggregatibacter actinomycetemcomitans‐induced alveolar bone loss

Madeira

Queiroz-Junior

Corrêa

et al. 2017

J Clinic Periodontology

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“…Lipoxygenase (LOX) inhibitors have been found to suppress osteoclast formation and enhance bone formation in vivo ( 8 , 9 ). A LOX inhibitor, Baicalein, which is extracted from the plant Scutellaria baicalensis inhibits 12- and 15-Lipoxygenase ( 12 - and 15-LOX ).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Lipoxygenases Showed No Benefit for the Musculoskeletal System in Estrogen Deficient Rats

Saul

Hohl²,

Franz³

et al. 2021

Front. Endocrinol.

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BackgroundIn previous studies, we reported the beneficial impact of two lipoxygenase-inhibitors, Baicalein and Zileuton, on osteoporotic bone in a postmenopausal rat model. Whereas subcutaneous Baicalein predominantly improved cortical bone, Zileuton enhanced vertebral and femoral trabecular bone. In this study, we aimed to reveal whether the oral administration of Baicalein caused similar effects on bone and whether a combined administration of Baicalein and Zileuton could act synergistically to ameliorate the formerly reported effects in the musculoskeletal system.MethodsWe treated ovariectomized (OVX) female Sprague-Dawley rats either with Baicalein (10mg/kg BW), Zileuton (10mg/kg BW) or a combination of both (each 10mg/kg BW) for 13 weeks and compared with untreated OVX and NON-OVX groups (n=12-16 rats per group). Lumbar vertebral bodies and femora were analyzed. Tibiae were osteotomized, plate-stabilized (at week 8 after OVX) and likewise analyzed by biomechanical, histological, micro-computed tomographical and ashing tests. The skeletal muscle structure was analyzed.ResultsOral administration of Baicalein did not confirm the reported favorable cortical effects in neither vertebra nor femur. Zileuton showed a beneficial effect on trabecular vertebra, while the femur was negatively affected. Callus formation was enhanced by all treatments; however, its density and biomechanical properties were unaltered. Lipoxygenase inhibition did not show a beneficial effect on skeletal muscle. The combination therapy did not ameliorate OVX-induced osteoporosis but induced even more bone loss.ConclusionsThe preventive anti-osteoporotic treatments with two lipoxygenase inhibitors applied either alone or in combination showed no benefit for the musculoskeletal system in estrogen deficient rats.

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Local inhibition of 5-lipoxygenase enhances bone formation in a rat model

Cited by 15 publications

References 45 publications

Effect of the lipoxygenase inhibitor baicalein on bone tissue and bone healing in ovariectomized rats

Effect of the lipoxygenase inhibitor baicalein on bone tissue and bone healing in ovariectomized rats

The role of 5‐lipoxygenase in Aggregatibacter actinomycetemcomitans‐induced alveolar bone loss

Inhibition of Lipoxygenases Showed No Benefit for the Musculoskeletal System in Estrogen Deficient Rats

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