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Recent evidence suggests an association between age‐related osteoporosis and cellular senescence in the bone; however, the specific bone cells that play a critical role in age‐related osteoporosis and the mechanism remain unknown. Results revealed that age‐related osteoporosis is characterized by the loss of osteoblast Men1. Osteoblast‐specific inducible knockout of Men1 caused structural changes in the mice bones, matching the phenotypes in patients with age‐related osteoporosis. Histomorphometrically, Men1‐knockout mice femurs decreased osteoblastic activity and increased osteoclastic activity, hallmarks of age‐related osteoporosis. Loss of Men1 induces cellular senescence via mTORC1 activation and AMPK suppression, rescued by metformin treatment. In bone morphogenetic protein‐indued bone model, loss of Men1 leads to accumulation of senescent cells and osteoporotic bone formation, which are ameliorated by metformin. Our results indicate that cellular senescence in osteoblasts plays a critical role in age‐related osteoporosis and that osteoblast‐specific inducible Men1‐knockout mice offer a promising model for developing therapeutics for age‐related osteoporosis. [ABSTRACT FROM AUTHOR]

The article discusses the study on the relationship of L-amino acid ligase called rizA in rhizocticin biosynthesis. The study performs series of analysis of unknown regions around rizA and create a new gene that encodes protein with adenosine triphosphate (ATP)-grasp motif upstream of rizA, called rizB. The results show that peptides of varying lengths were synthesized and unknown L-amino acid ligases that are catalyzing oligopeptide synthesis are existing in other microorganisms.

Arthritis is inflammation of the joints accompanied by osteochondral destruction. It can take many forms, including osteoarthritis, rheumatoid arthritis, and psoriatic arthritis. These diseases share one commonality—osteochondral destruction based on inflammation. The background includes a close interaction between osseous tissues and immune cells through various inflammatory cytokines. However, the tissues and cytokines that play major roles are different in each disease, and as a result, the mechanism of osteochondral destruction also differs. In recent years, there have been many findings regarding not only extracellular signaling pathways but also intracellular signaling pathways. In particular, we anticipate that the intracellular signals of osteoclasts, which play a central role in bone destruction, will become novel therapeutic targets. In this review, we have summarized the pathology of arthritis and the latest findings on the mechanism of osteochondral destruction, as well as present and future therapeutic strategies for these targets. [ABSTRACT FROM AUTHOR]

Background: Nonunion following fracture treatment remains a significant clinical challenge, adversely affecting the patient's quality of life and imposing a substantial economic burden. The emergence of bone morphogenetic protein 2 (BMP-2) for bone regeneration represents a promising avenue, albeit limited by side effects such as inflammatory reactions primarily due to suboptimal drug delivery systems. This study focuses on NOVOSIS putty (NP), a novel biomaterial designed for the sustained release of BMP-2, aiming to mitigate these limitations and enhance bone healing., Objective: This research aimed to evaluate the effectiveness of NP, a hydroxyapatite granules/β-tricalcium phosphate hydrogel composite (HA/β-TCP/hydrogel), as a BMP-2 carrier for promoting bone regeneration in a new rat nonunion model of long bone., Methods: Using Sprague Dawley rats, a 2-mm silicone disk was interposed at the femoral fracture site, and intramedullary fixation with K-wire was performed to create a nonunion with a 2-mm bone defect. After 3 weeks, internal fixation with a plate, removal of the silicon disk, and refreshing the nonunion site were performed by implanting three different materials into the nonunion sites: allogenic iliac bone (IB), collagen sponge (CS) containing 10 μg of BMP-2, or NP containing 10 μg of BMP-2. Bone healing was evaluated weekly using micro-computed tomography (CT); ex vivo micro-Ct and histological evaluation were conducted at 6 weeks., Results: At 6 weeks, NP demonstrated a significantly higher bone union rate (76.5%) compared with the CS group (35.3%, p = 0.037), and the IB group (6.3%, p < 0.0001). Bone mineral density (BMD) and bone volume/tissue volume (BV/TV) were also significantly higher in the NP group compared with the CS group (BMD, p < 0.0001; BV/TV, p = 0.031). Histological analysis showed the fracture gap in the NP group was filled with more trabecular bone and less fibrous tissue compared with the CS group., Conclusion: The study confirms NP is a highly effective BMP-2 carrier, significantly improving bone union rates and new bone formation in nonunion fractures. The sustained release of BMP-2 from the hydrogel component reduced inflammatory responses and enhanced bone regeneration. NP can be a promising alternative to collagen-based BMP-2 delivery systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kitahara, Tateiwa, Hirai, Ikuta, Furuichi, Bun, Ukon, Kanie, Furuya, Fujimori, Okada and Kaito.)

Bone tissue is regenerated via the spatiotemporal involvement of various cytokines. Among them, the bone morphogenetic protein (BMP), which plays a vital role in the bone regeneration process, has been applied clinically for the treatment of refractory orthopedic conditions. Although BMP therapy using a collagen carrier has shown efficiency in bone regeneration over the last two decades, a major challenge-considerable side effects associated with the acute release of high doses of BMPs-has also been revealed. To improve BMP efficiency, the development of new carriers and biologics that can be used in conjunction with BMPs is currently underway. In this review, we describe the current status and future prospects of bone regeneration therapy, with a focus on BMPs. Furthermore, we outline the characteristics and molecular signaling pathways involving BMPs, clinical applications of BMPs in orthopedics, clinical results of BMP use in human spinal surgeries, drugs combined with BMPs to provide synergistic effects, and novel BMP carriers., Competing Interests: Paid consultant for a company or supplier: Asahi Kasei Pharma, Kyocera, Medacta, Medtronic Sofamor Danek, NipponZoki Pharma, Nuvasive, TwoCell. Research support from a company or supplier as a PI: Aimedic MMT, Asahi Kasei Pharma, NipponZoki Pharma, PIP, SheepMedical, Twocell. Medical/Orthopaedic publications editorial/governing board: JOR Spine, NASSj, Neurospine. Board member/committee appointments for a society: Japanese Orthopaedic Association, Japanese Scoliosis Scoiety, Scoliosis Research Society, The Japanese Society for Spine Surgery and Related Research, The Japanese Spinal Instrumentation Society., (© 2022 The Author(s). Published by Elsevier Ltd on behalf of North American Spine Society.)