An antagonistic monoclonal anti–Plexin-B1 antibody exerts therapeutic effects in mouse models of postmenopausal osteoporosis and multiple sclerosis

Vogler, Melanie; Oleksy, Arkadiusz; Schulze, Sabrina; Fedorova, Marina; Kojonazarov, Baktybek; Nijjar, Sharandip; Patel, Seema; Jossi, Sian; Sawmynaden, Kovilen; Henry, Marie‐Claire; Brown, R. H.; Matthews, David J.; Offermanns, Stefan; Worzfeld, Thomas

doi:10.1016/j.jbc.2022.102265

Cited by 3 publications

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“…The plexin family member, Plexin-B1, is expressed by osteoblasts, while its high-affinity ligand, semaphorin 4D (Sema4D), localizes to osteoclasts ( 10 , 11 ). A 150-kDa glycoprotein transmembrane homodimer, Sema4D (CD100) - a member of the Semaphorin family - is a signaling protein implicated in axon-guiding processes.…”

Section: Discussionmentioning

confidence: 99%

Leptin and melatonin’s effects on OVX rodents’ bone metabolism

Lin

Xiong

et al. 2023

Front. Endocrinol.

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PurposeThis study aims to examine the effects of leptin and melatonin intervention on bone metabolism in ovariectomize (OVX) rodents, as well as their potential mechanisms of action.MethodsPrepare an OVX model of osteoporosis in rodents and validate the model by collecting bilateral tibia samples for Micro-CT scanning and histological analysis. A control group of normal size, the OVX group, the OVX+Sema4D (Semaphorin 4D) group, the OVX+Sema4D+Leptin group, the OVX+Sema4D+ Melatonin(MT) group and the OVX+Sema4D+Leptin+ MT group were the experimental groups. Adenovirus vector construction and tibial medullary injection validation were conducted in accordance with the aforementioned experimental groups. Four groups of rats were injected with the Sema4D overexpression adenovirus vector into the tibial medullary cavity, and two groups were injected with the Leptin overexpression adenovirus vector. The repair of osteoporosis was observed using micro-CT and histological analysis. Immunohistochemical detection of bone morphogenetic protein-2 (BMP-2) expression in bone tissue was employed to ascertain the amount of osteoclasts in the upper tibial metaphysis, utilizing TRAP(tartrate-resistant acid phosphatase) staining.ResultsIncreased levels of BV/TV, Tb.N, BMD, and BMC were seen in the OVX+ Sema4D+Leptin, OVX+ Sema4D+MT, and OVX+ Sema4D+Leptin+ MT groups compared to the OVX group, whereas Tb. Sp levels were lowered. When compared to the Sema4D overexpression group, the trabecular bone structure of the OVX + Sema4D + Leptin, OVX + Sema4D + MT, and OVX + Sema4D + Leptin + MT groups is largely intact, tends to be closer, and the amount of trabecular bone increases. The OVX + Sema4D + Leptin + MT group in particular.The expression of BMP-2 was dramatically upregulated (p<0.05), the number of TRAP-stained osteoclasts was significantly reduced (p<0.05), and BALP(bone-derived alkaline phosphatase) and TRAP-5b(tartrate-resistant acid phosphatase-5b) activities were significantly downregulated (p<0.05).ConclusionIn rats with osteoporosis, leptin and melatonin can be seen to augment the trabecular microstructure of the bone, augment bone growth, diminish trabecular harm, and mend the bone. The combined effect is more powerful.

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Section: Discussionmentioning

confidence: 99%

Leptin and melatonin’s effects on OVX rodents’ bone metabolism

Lin

Xiong

et al. 2023

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…Therapeutic targeting of the plexin-B:semaphorin interaction has been suggested as a mechanism for the treatment of several conditions, including cancer, multiple sclerosis, osteoporosis ( 24 , 25 ) and diabetic retinopathy ( 26 ). A monoclonal antibody targeted on Sema4D, VX15/2503 (Pepinemab), has completed phase 2 trials for the treatment of non-small-cell lung carcinoma in combination with avelumab ( Clinicaltrials.gov identifier: NCT03268057).…”

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confidence: 99%